rs840016

Positions:

• chr1-167439433-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000470379.2(CD247):​c.-156G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,610,448 control chromosomes in the GnomAD database, including 114,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (7494 hom., cov: 33)
  • Exomes 𝑓: 0.37 (107218 hom.)
• Consequence: CD247 ENST00000470379.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.535

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-167439433-C-T is Benign according to our data. Variant chr1-167439433-C-T is described in ClinVar as [Benign]. Clinvar id is 1179252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD247	NM_198053.3	c.163-33G>A		intron_variant		ENST00000362089.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD247	ENST00000362089.10	c.163-33G>A		intron_variant		1	NM_198053.3	A1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43010 AN: 152132 Hom.: 7499 Cov.: 33

Gnomad AFR AF: 0.0879

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.325

GnomAD3 exomes AF: 0.311 AC: 77777 AN: 250192 Hom.: 13782 AF XY: 0.323 AC XY: 43735 AN XY: 135410

Gnomad AFR exome AF: 0.0805

Gnomad AMR exome AF: 0.236

Gnomad ASJ exome AF: 0.482

Gnomad EAS exome AF: 0.105

Gnomad SAS exome AF: 0.298

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.399

Gnomad OTH exome AF: 0.358

GnomAD4 exome AF: 0.373 AC: 543787 AN: 1458198 Hom.: 107218 Cov.: 31 AF XY: 0.373 AC XY: 270325 AN XY: 725622

Gnomad4 AFR exome AF: 0.0774

Gnomad4 AMR exome AF: 0.240

Gnomad4 ASJ exome AF: 0.478

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.301

Gnomad4 FIN exome AF: 0.253

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.363

GnomAD4 genome AF: 0.282 AC: 42994 AN: 152250 Hom.: 7494 Cov.: 33 AF XY: 0.274 AC XY: 20367 AN XY: 74432

Gnomad4 AFR AF: 0.0877

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.321

Alfa AF: 0.377 Hom.: 14411

Bravo AF: 0.276

Asia WGS AF: 0.163 AC: 563 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 35% of patients studied by a panel of primary immunodeficiencies. Number of patients: 34. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Benign	0.91

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: rs840016; hg19: chr1-167408670; COSMIC: COSV62980812; COSMIC: COSV62980812;