NM_005214.5:c.*528_*571delATATATATATATATATATATATATATATATATATATATATATAT

Variant names:

• chr2-203873327-CATATATATATATATATATATATATATATATATATATATATATAT-C
• rs60872763
• NM_005214.5:c.*528_*571delATATATATATATATATATATATATATATATATATATATATATAT

Variant summary

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

The NM_005214.5(CTLA4):​c.*528_*571delATATATATATATATATATATATATATATATATATATATATATAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 181,422 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0036 (1 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 amr. gnomad4 allele frequency = 0.0000655 (8/122094) while in subpopulation AMR AF= 0.000244 (3/12288). AF 95% confidence interval is 0.0000664. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTLA4	NM_005214.5	c.*528_*571delATATATATATATATATATATATATATATATATATATATATATAT		3_prime_UTR_variant	Exon 4 of 4	ENST00000648405.2	NP_005205.2
CTLA4	NM_001037631.3	c.*565_*608delATATATATATATATATATATATATATATATATATATATATATAT		3_prime_UTR_variant	Exon 3 of 3		NP_001032720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTLA4	ENST00000648405.2	c.*528_*571delATATATATATATATATATATATATATATATATATATATATATAT		3_prime_UTR_variant	Exon 4 of 4		NM_005214.5	ENSP00000497102.1
CTLA4	ENST00000696479.1	c.*528_*571delATATATATATATATATATATATATATATATATATATATATATAT		3_prime_UTR_variant	Exon 5 of 5			ENSP00000512655.1
CTLA4	ENST00000696049.1	c.*516_*559delATATATATATATATATATATATATATATATATATATATATATAT		downstream_gene_variant				ENSP00000512353.1
CTLA4	ENST00000427473.3	n.*238_*281delATATATATATATATATATATATATATATATATATATATATATAT		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0000655 AC: 8 AN: 122102 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000677

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000244

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000172

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000334

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00357 AC: 212 AN: 59328 Hom.: 1 AF XY: 0.00371 AC XY: 111 AN XY: 29936

Gnomad4 AFR exome AF: 0.00259

Gnomad4 AMR exome AF: 0.00415

Gnomad4 ASJ exome AF: 0.00311

Gnomad4 EAS exome AF: 0.00148

Gnomad4 SAS exome AF: 0.00242

Gnomad4 FIN exome AF: 0.00214

Gnomad4 NFE exome AF: 0.00382

Gnomad4 OTH exome AF: 0.00463

GnomAD4 genome AF: 0.0000655 AC: 8 AN: 122094 Hom.: 0 Cov.: 0 AF XY: 0.0000515 AC XY: 3 AN XY: 58196

Gnomad4 AFR AF: 0.0000676

Gnomad4 AMR AF: 0.000244

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000172

Gnomad4 NFE AF: 0.0000334

Gnomad4 OTH AF: 0.00

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;