2-203873327-CATATATATATATATATATATATATATATATATATATATATATATAT-CATAT

Position:

• chr2-203873327-CATATATATATATATATATATATATATATATATATATATATATATAT-CATAT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_005214.5(CTLA4):​c.*530_*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 0.579 in 184,200 control chromosomes in the GnomAD database, including 33,300 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (12373 hom., cov: 0)
  • Exomes 𝑓: 0.83 (20927 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.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTLA4	NM_005214.5	c.*530_*571del		3_prime_UTR_variant	4/4	ENST00000648405.2
CTLA4	NM_001037631.3	c.*567_*608del		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTLA4	ENST00000648405.2	c.*530_*571del		3_prime_UTR_variant	4/4		NM_005214.5	P1
CTLA4	ENST00000696479.1	c.*530_*571del		3_prime_UTR_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.453 AC: 55768 AN: 122980 Hom.: 12371 Cov.: 0

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.625

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.509

GnomAD4 exome AF: 0.831 AC: 50904 AN: 61230 Hom.: 20927 AF XY: 0.830 AC XY: 25624 AN XY: 30884

Gnomad4 AFR exome AF: 0.722

Gnomad4 AMR exome AF: 0.811

Gnomad4 ASJ exome AF: 0.848

Gnomad4 EAS exome AF: 0.671

Gnomad4 SAS exome AF: 0.882

Gnomad4 FIN exome AF: 0.897

Gnomad4 NFE exome AF: 0.848

Gnomad4 OTH exome AF: 0.837

GnomAD4 genome AF: 0.453 AC: 55760 AN: 122970 Hom.: 12373 Cov.: 0 AF XY: 0.461 AC XY: 27026 AN XY: 58656

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.498

Gnomad4 OTH AF: 0.511

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;