2-203873327-CATATATATATATATATATATATATATATATATATATATATATATAT-CATATATATATATATATATATATAT

Position:

• chr2-203873327-CATATATATATATATATATATATATATATATATATATATATATATAT-CATATATATATATATATATATATAT

Variant summary

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

The NM_005214.5(CTLA4):​c.*550_*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 0.0332 in 182,254 control chromosomes in the GnomAD database, including 186 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.046 (186 hom., cov: 0)
  • Exomes 𝑓: 0.0080 (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.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTLA4	NM_005214.5	c.*550_*571del		3_prime_UTR_variant	4/4	ENST00000648405.2
CTLA4	NM_001037631.3	c.*587_*608del		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTLA4	ENST00000648405.2	c.*550_*571del		3_prime_UTR_variant	4/4		NM_005214.5	P1
CTLA4	ENST00000696479.1	c.*550_*571del		3_prime_UTR_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.0456 AC: 5555 AN: 121730 Hom.: 184 Cov.: 0

Gnomad AFR AF: 0.0809

Gnomad AMI AF: 0.00501

Gnomad AMR AF: 0.0363

Gnomad ASJ AF: 0.0355

Gnomad EAS AF: 0.0675

Gnomad SAS AF: 0.0263

Gnomad FIN AF: 0.0200

Gnomad MID AF: 0.0317

Gnomad NFE AF: 0.0339

Gnomad OTH AF: 0.0384

GnomAD4 exome AF: 0.00804 AC: 487 AN: 60536 Hom.: 0 AF XY: 0.00835 AC XY: 255 AN XY: 30536

Gnomad4 AFR exome AF: 0.0154

Gnomad4 AMR exome AF: 0.00754

Gnomad4 ASJ exome AF: 0.00577

Gnomad4 EAS exome AF: 0.0178

Gnomad4 SAS exome AF: 0.00595

Gnomad4 FIN exome AF: 0.00280

Gnomad4 NFE exome AF: 0.00718

Gnomad4 OTH exome AF: 0.00771

GnomAD4 genome AF: 0.0457 AC: 5560 AN: 121718 Hom.: 186 Cov.: 0 AF XY: 0.0447 AC XY: 2594 AN XY: 57992

Gnomad4 AFR AF: 0.0810

Gnomad4 AMR AF: 0.0364

Gnomad4 ASJ AF: 0.0355

Gnomad4 EAS AF: 0.0673

Gnomad4 SAS AF: 0.0260

Gnomad4 FIN AF: 0.0200

Gnomad4 NFE AF: 0.0339

Gnomad4 OTH AF: 0.0375

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;