2-203873327-CATATATATATATATATATATATATATATATATATATATATATATAT-CATATATATATATATATATATATATATATATATATATATATAT

Position:

• chr2-203873327-CATATATATATATATATATATATATATATATATATATATATATATAT-CATATATATATATATATATATATATATATATATATATATATAT

Variant summary

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

The NM_005214.5(CTLA4):​c.*568_*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 0.00236 in 182,306 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0035 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000016 (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 = 0.00354 (429/121086) while in subpopulation AFR AF= 0.00477 (140/29326). AF 95% confidence interval is 0.00413. There are 0 homozygotes in gnomad4. There are 184 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 429 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTLA4	NM_005214.5	c.*568_*571del		3_prime_UTR_variant	4/4	ENST00000648405.2
CTLA4	NM_001037631.3	c.*605_*608del		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTLA4	ENST00000648405.2	c.*568_*571del		3_prime_UTR_variant	4/4		NM_005214.5	P1
CTLA4	ENST00000696479.1	c.*568_*571del		3_prime_UTR_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.00354 AC: 429 AN: 121092 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00478

Gnomad AMI AF: 0.00127

Gnomad AMR AF: 0.00172

Gnomad ASJ AF: 0.00349

Gnomad EAS AF: 0.000708

Gnomad SAS AF: 0.00185

Gnomad FIN AF: 0.000519

Gnomad MID AF: 0.00410

Gnomad NFE AF: 0.00391

Gnomad OTH AF: 0.00528

GnomAD4 exome AF: 0.0000163 AC: 1 AN: 61220 Hom.: 0 AF XY: 0.0000324 AC XY: 1 AN XY: 30882

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: 0.0000234

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00354 AC: 429 AN: 121086 Hom.: 0 Cov.: 0 AF XY: 0.00319 AC XY: 184 AN XY: 57758

Gnomad4 AFR AF: 0.00477

Gnomad4 AMR AF: 0.00172

Gnomad4 ASJ AF: 0.00349

Gnomad4 EAS AF: 0.000712

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.000519

Gnomad4 NFE AF: 0.00391

Gnomad4 OTH AF: 0.00523

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;