chr1-167438621-G-A

Variant names:

• chr1-167438621-G-A
• rs33937946
• ENST00000470379.2:c.-37C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000470379.2(CD247):​c.-37C>T variant causes a 5 prime UTR premature start codon gain 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 ENST00000470379.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.07
• Publications: 6 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 -20 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 VariationId is 466354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
CD247	NM_198053.3	c.249C>T	p.Tyr83Tyr	synonymous_variant	Exon 4 of 8	ENST00000362089.10	NP_932170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD247	ENST00000362089.10	c.249C>T	p.Tyr83Tyr	synonymous_variant	Exon 4 of 8	1	NM_198053.3	ENSP00000354782.5

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

GnomAD2 exomes AF: 0.0386 AC: 9699 AN: 251490 AF XY: 0.0354

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 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

African (AFR) AF: 0.163 AC: 5440 AN: 33432

American (AMR) AF: 0.0297 AC: 1327 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0455 AC: 1189 AN: 26134

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.00878 AC: 757 AN: 86252

European-Finnish (FIN) AF: 0.0229 AC: 1221 AN: 53418

Middle Eastern (MID) AF: 0.0479 AC: 276 AN: 5766

European-Non Finnish (NFE) AF: 0.0411 AC: 45642 AN: 1111242

Other (OTH) AF: 0.0428 AC: 2581 AN: 60358

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

African (AFR) AF: 0.154 AC: 6372 AN: 41452

American (AMR) AF: 0.0400 AC: 612 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 160 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00934 AC: 45 AN: 4818

European-Finnish (FIN) AF: 0.0223 AC: 236 AN: 10604

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0411 AC: 2799 AN: 68020

Other (OTH) AF: 0.0630 AC: 133 AN: 2110

Alfa AF: 0.0483 Hom.: 590

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Immunodeficiency 25 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.49
DANN	Benign	0.64
PhyloP100		-1.1
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		1.0
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: rs33937946; hg19: chr1-167407858;