2-203873327-CATATATATATATATATATATATATATATATATATATATATATATAT-CATATATATATATATATATATATATATATATATATAT

Position:

• chr2-203873327-CATATATATATATATATATATATATATATATATATATATATATATAT-CATATATATATATATATATATATATATATATATATAT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_005214.5(CTLA4):​c.*562_*571del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00329 in 182,736 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0049 (2 hom., cov: 0)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: CTLA4 NM_005214.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83

Genes affected

CTLA4 (HGNC:2505): (cytotoxic T-lymphocyte associated protein 4) This gene is a member of the immunoglobulin superfamily and encodes a protein which transmits an inhibitory signal to T cells. The protein contains a V domain, a transmembrane domain, and a cytoplasmic tail. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. The membrane-bound isoform functions as a homodimer interconnected by a disulfide bond, while the soluble isoform functions as a monomer. Mutations in this gene have been associated with insulin-dependent diabetes mellitus, Graves disease, Hashimoto thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, and other autoimmune diseases. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00489 (594/121548) while in subpopulation AFR AF= 0.00868 (255/29380). AF 95% confidence interval is 0.0078. There are 2 homozygotes in gnomad4. There are 273 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 594 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTLA4	NM_005214.5	c.*562_*571del		3_prime_UTR_variant	4/4	ENST00000648405.2
CTLA4	NM_001037631.3	c.*599_*608del		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTLA4	ENST00000648405.2	c.*562_*571del		3_prime_UTR_variant	4/4		NM_005214.5	P1
CTLA4	ENST00000696479.1	c.*562_*571del		3_prime_UTR_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.00490 AC: 596 AN: 121558 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00872

Gnomad AMI AF: 0.00125

Gnomad AMR AF: 0.00302

Gnomad ASJ AF: 0.00283

Gnomad EAS AF: 0.00307

Gnomad SAS AF: 0.000922

Gnomad FIN AF: 0.00138

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00437

Gnomad OTH AF: 0.00408

GnomAD4 exome AF: 0.000131 AC: 8 AN: 61188 Hom.: 0 AF XY: 0.0000972 AC XY: 3 AN XY: 30864

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000188

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00489 AC: 594 AN: 121548 Hom.: 2 Cov.: 0 AF XY: 0.00471 AC XY: 273 AN XY: 57932

Gnomad4 AFR AF: 0.00868

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00283

Gnomad4 EAS AF: 0.00308

Gnomad4 SAS AF: 0.000925

Gnomad4 FIN AF: 0.00138

Gnomad4 NFE AF: 0.00438

Gnomad4 OTH AF: 0.00405

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs60872763; hg19: chr2-204738050;