2-203873327-CATATATATATATATATATATATATATATATATATATATATATATAT-CATATATATATATATATATATATATAT

Position:

• chr2-203873327-CATATATATATATATATATATATATATATATATATATATATATATAT-CATATATATATATATATATATATATAT

Variant summary

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

The NM_005214.5(CTLA4):​c.*552_*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 0.0198 in 182,616 control chromosomes in the GnomAD database, including 57 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.028 (57 hom., cov: 0)
  • Exomes 𝑓: 0.0031 (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 = 0.0528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTLA4	NM_005214.5	c.*552_*571del		3_prime_UTR_variant	4/4	ENST00000648405.2
CTLA4	NM_001037631.3	c.*589_*608del		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTLA4	ENST00000648405.2	c.*552_*571del		3_prime_UTR_variant	4/4		NM_005214.5	P1
CTLA4	ENST00000696479.1	c.*552_*571del		3_prime_UTR_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.0282 AC: 3427 AN: 121712 Hom.: 56 Cov.: 0

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.0414

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.0379

Gnomad EAS AF: 0.0366

Gnomad SAS AF: 0.0132

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.0476

Gnomad NFE AF: 0.0168

Gnomad OTH AF: 0.0268

GnomAD4 exome AF: 0.00310 AC: 189 AN: 60914 Hom.: 0 AF XY: 0.00319 AC XY: 98 AN XY: 30710

Gnomad4 AFR exome AF: 0.00846

Gnomad4 AMR exome AF: 0.00252

Gnomad4 ASJ exome AF: 0.00305

Gnomad4 EAS exome AF: 0.00650

Gnomad4 SAS exome AF: 0.00239

Gnomad4 FIN exome AF: 0.00349

Gnomad4 NFE exome AF: 0.00270

Gnomad4 OTH exome AF: 0.00225

GnomAD4 genome AF: 0.0282 AC: 3427 AN: 121702 Hom.: 57 Cov.: 0 AF XY: 0.0273 AC XY: 1583 AN XY: 58000

Gnomad4 AFR AF: 0.0550

Gnomad4 AMR AF: 0.0171

Gnomad4 ASJ AF: 0.0379

Gnomad4 EAS AF: 0.0363

Gnomad4 SAS AF: 0.0130

Gnomad4 FIN AF: 0.0300

Gnomad4 NFE AF: 0.0168

Gnomad4 OTH AF: 0.0266

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;