2-203873327-CATATATATATATATATATATATATATATATATATATATATATATAT-CATATATATATATATATATATATATATAT

Position:

• chr2-203873327-CATATATATATATATATATATATATATATATATATATATATATATAT-CATATATATATATATATATATATATATAT

Variant summary

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

The NM_005214.5(CTLA4):​c.*554_*571delATATATATATATATATAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 182,656 control chromosomes in the GnomAD database, including 32 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.018 (32 hom., cov: 0)
  • Exomes 𝑓: 0.00084 (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 = 0.0175 (2133/121632) while in subpopulation AFR AF= 0.0311 (915/29378). AF 95% confidence interval is 0.0295. There are 32 homozygotes in gnomad4. There are 915 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2133 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTLA4	NM_005214.5	c.*554_*571delATATATATATATATATAT		3_prime_UTR_variant	4/4	ENST00000648405.2	NP_005205.2
CTLA4	NM_001037631.3	c.*591_*608delATATATATATATATATAT		3_prime_UTR_variant	3/3		NP_001032720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTLA4	ENST00000648405.2	c.*554_*571delATATATATATATATATAT		3_prime_UTR_variant	4/4		NM_005214.5	ENSP00000497102.1
CTLA4	ENST00000696479.1	c.*554_*571delATATATATATATATATAT		3_prime_UTR_variant	5/5			ENSP00000512655.1

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2128 AN: 121640 Hom.: 32 Cov.: 0

Gnomad AFR AF: 0.0310

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.0154

Gnomad EAS AF: 0.00352

Gnomad SAS AF: 0.00161

Gnomad FIN AF: 0.00241

Gnomad MID AF: 0.00400

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.000836 AC: 51 AN: 61024 Hom.: 0 AF XY: 0.000813 AC XY: 25 AN XY: 30766

Gnomad4 AFR exome AF: 0.00168

Gnomad4 AMR exome AF: 0.00150

Gnomad4 ASJ exome AF: 0.000303

Gnomad4 EAS exome AF: 0.00103

Gnomad4 SAS exome AF: 0.00119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000846

Gnomad4 OTH exome AF: 0.000450

GnomAD4 genome AF: 0.0175 AC: 2133 AN: 121632 Hom.: 32 Cov.: 0 AF XY: 0.0158 AC XY: 915 AN XY: 58010

Gnomad4 AFR AF: 0.0311

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.0154

Gnomad4 EAS AF: 0.00354

Gnomad4 SAS AF: 0.00162

Gnomad4 FIN AF: 0.00241

Gnomad4 NFE AF: 0.0143

Gnomad4 OTH AF: 0.0156

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;