Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_005214.5(CTLA4):c.615C>G (p.Pro205=)

CA2067158

741101 (ClinVar)

Gene: CTLA4 (HGNC:1493)

Condition: autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency (MONDO:0014493)

Inheritance Mode: Autosomal dominant inheritance

UUID: 0c9d5cdf-c9d0-4199-857c-8b46e4dc779a

Approved on: 2025-11-24

Published on: 2025-12-02

HGVS expressions

NM_005214.5:c.615C>G

NM_005214.5(CTLA4):c.615C>G (p.Pro205=)

NC_000002.12:g.203872755C>G

CM000664.2:g.203872755C>G

NC_000002.11:g.204737478C>G

CM000664.1:g.204737478C>G

NC_000002.10:g.204445723C>G

NG_011502.1:g.9970C>G

ENST00000696049.1:c.555C>G

ENST00000696479.1:c.687C>G

ENST00000427473.3:n.539C>G

ENST00000648405.2:c.615C>G

ENST00000650075.1:n.639C>G

ENST00000295854.10:c.505C>G

ENST00000302823.7:c.615C>G

ENST00000427473.2:c.394C>G

ENST00000472206.1:c.220C>G

ENST00000487393.1:n.157C>G

NM_001037631.2:c.505C>G

NM_005214.4:c.615C>G

NM_001037631.3:c.505C>G

Benign

BA1 BP7 BP4

PP3

Evidence Links 0

Expert Panel

Antibody Deficiencies VCEP

Criteria Specification Information

Criteria Specification: ClinGen Antibody Deficiencies Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CTLA4 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Antibody Deficiencies VCEP

NM_005214.5(CTLA4):c.615C>G (p.Pro205=) is a synonymous variant in exon 2 that does not have a predicted impact at splicing sites (BP7). The splicing impact predictor SpliceAI gives a delta score of 0.03 for acceptor gain, which is below the ClinGen Antibody Deficiencies VCEP recommended threshold of <0.1 and does not strongly predict an impact on splicing (BP4). This variant is present in gnomAD v4.1.0 at a GrpMax allele frequency of 0.0004811, with 30 alleles / 44,874 total alleles in the East Asian population, which is higher than the ClinGen Antibody Deficiencies VCEP BA1 threshold of >0.0000111 (BA1). In summary, this variant meets the criteria to be classified as benign for autosomal dominant autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Antibody Deficiencies VCEP: BA1, BP4, and BP7. (VCEP specifications version 1.0.0; date of approval 09/18/2025).

BA1

This variant is present in gnomAD v4.1.0 at a GrpMax allele frequency of 0.0004811, with 30 alleles / 44,874 total alleles in the East Asian population, which is higher than the ClinGen Antibody Deficiencies VCEP BA1 threshold of >0.0000111 (BA1).

BP7

The synonymous variant NM_005214.5(CTLA4):c.615C>G (p.Pro205=) does not have a predicted impact at splicing sites (BP7).

BP4

The splicing impact predictor SpliceAI gives a delta score of 0.03 for acceptor gain, which is below the ClinGen Antibody Deficiencies VCEP recommended threshold of <0.1 and does not strongly predict an impact on splicing (BP4).

PP3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

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