rs33937946

chr1-167438621-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_198053.3(CD247):c.249C>T(p.Tyr83=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 1,613,172 control chromosomes in the GnomAD database, including 2,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (595 hom., cov: 32)
  • Exomes 𝑓: 0.040 (1589 hom.)
• Consequence: CD247 NM_198053.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.07

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 1-167438621-G-A is Benign according to our data. Variant chr1-167438621-G-A is described in ClinVar as [Benign]. Clinvar id is 466354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-167438621-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD247	NM_198053.3	c.249C>T	p.Tyr83=	synonymous_variant	4/8	ENST00000362089.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD247	ENST00000362089.10	c.249C>T	p.Tyr83=	synonymous_variant	4/8	1	NM_198053.3	A1

Frequencies

GnomAD3 genomes AF: 0.0682 AC: 10362 AN: 152030 Hom.: 591 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0401

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00954

Gnomad FIN AF: 0.0223

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0411

Gnomad OTH AF: 0.0637

GnomAD3 exomes AF: 0.0386 AC: 9699 AN: 251490 Hom.: 342 AF XY: 0.0354 AC XY: 4807 AN XY: 135920

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.0273

Gnomad ASJ exome AF: 0.0448

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00817

Gnomad FIN exome AF: 0.0234

Gnomad NFE exome AF: 0.0416

Gnomad OTH exome AF: 0.0414

GnomAD4 exome AF: 0.0400 AC: 58436 AN: 1461024 Hom.: 1589 Cov.: 32 AF XY: 0.0386 AC XY: 28065 AN XY: 726870

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.0297

Gnomad4 ASJ exome AF: 0.0455

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00878

Gnomad4 FIN exome AF: 0.0229

Gnomad4 NFE exome AF: 0.0411

Gnomad4 OTH exome AF: 0.0428

GnomAD4 genome AF: 0.0682 AC: 10374 AN: 152148 Hom.: 595 Cov.: 32 AF XY: 0.0651 AC XY: 4839 AN XY: 74378

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.0400

Gnomad4 ASJ AF: 0.0461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00934

Gnomad4 FIN AF: 0.0223

Gnomad4 NFE AF: 0.0411

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.0532 Hom.: 232

Bravo AF: 0.0749

Asia WGS AF: 0.0150 AC: 53 AN: 3478

EpiCase AF: 0.0450

EpiControl AF: 0.0456

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Immunodeficiency 25 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	0.49
Dann	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs33937946; hg19: chr1-167407858;