rs1052231

Variant names:

• chr1-167430837-T-A
• rs1052231
• NM_198053.3:c.*844A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-167430837-T-A
• chr1-167430837-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198053.3(CD247):​c.*844A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 398,660 control chromosomes in the GnomAD database, including 136,198 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.82 (51239 hom., cov: 35)
  • Exomes 𝑓: 0.83 (84959 hom.)
• Consequence: CD247 NM_198053.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180
• Publications: 18 publications found

Genes affected

CD247 (HGNC:1677): (CD247 molecule) The protein encoded by this gene is T-cell receptor zeta, which together with T-cell receptor alpha/beta and gamma/delta heterodimers, and with CD3-gamma, -delta and -epsilon, forms the T-cell receptor-CD3 complex. The zeta chain plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. Low expression of the antigen results in impaired immune response. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CD247 Gene-Disease associations (from GenCC):

• immunodeficiency 25

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD247	NM_198053.3	c.*844A>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000362089.10	NP_932170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD247	ENST00000362089.10	c.*844A>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_198053.3	ENSP00000354782.5

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124589 AN: 152164 Hom.: 51196 Cov.: 35

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.839

GnomAD4 exome AF: 0.830 AC: 204472 AN: 246378 Hom.: 84959 Cov.: 0 AF XY: 0.830 AC XY: 103598 AN XY: 124840

African (AFR) AF: 0.758 AC: 5443 AN: 7182

American (AMR) AF: 0.864 AC: 6427 AN: 7436

Ashkenazi Jewish (ASJ) AF: 0.860 AC: 7945 AN: 9242

East Asian (EAS) AF: 0.756 AC: 17301 AN: 22894

South Asian (SAS) AF: 0.875 AC: 2654 AN: 3032

European-Finnish (FIN) AF: 0.854 AC: 17790 AN: 20830

Middle Eastern (MID) AF: 0.854 AC: 1105 AN: 1294

European-Non Finnish (NFE) AF: 0.836 AC: 132129 AN: 158096

Other (OTH) AF: 0.835 AC: 13678 AN: 16372

GnomAD4 genome AF: 0.819 AC: 124685 AN: 152282 Hom.: 51239 Cov.: 35 AF XY: 0.821 AC XY: 61127 AN XY: 74466

African (AFR) AF: 0.759 AC: 31530 AN: 41534

American (AMR) AF: 0.860 AC: 13159 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2977 AN: 3472

East Asian (EAS) AF: 0.765 AC: 3961 AN: 5178

South Asian (SAS) AF: 0.869 AC: 4193 AN: 4826

European-Finnish (FIN) AF: 0.860 AC: 9129 AN: 10618

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.836 AC: 56902 AN: 68032

Other (OTH) AF: 0.840 AC: 1776 AN: 2114

Alfa AF: 0.826 Hom.: 6475

Bravo AF: 0.816

Asia WGS AF: 0.807 AC: 2806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.35
DANN	Benign	0.59
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1052231; hg19: chr1-167400074;