Variant rs952963 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198053.3(CD247):c.393+45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,530,668 control chromosomes in the GnomAD database, including 10,830 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1585 hom., cov: 33)

Exomes 𝑓: 0.11 ( 9245 hom. )

Consequence

CD247
NM_198053.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.940

Variant links:

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 links:

CD247 (HGNC:):

CD247 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-167433975-G-A is Benign according to our data. Variant chr1-167433975-G-A is described in ClinVar as [Benign]. Clinvar id is 1265565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD247	NM_198053.3 linkuse as main transcript	c.393+45C>T		intron_variant		ENST00000362089.10	NP_932170.1	P20963-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD247	ENST00000362089.10 linkuse as main transcript	c.393+45C>T		intron_variant		1	NM_198053.3	ENSP00000354782.5		P20963-1

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20824

AN:

152118

Hom.:

1584

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.0806

Gnomad EAS

AF:

0.233

Gnomad SAS

AF:

0.0902

Gnomad FIN

AF:

0.0889

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.128

GnomAD3 exomes

AF:

0.117

AC:

29467

AN:

251472

Hom.:

1951

AF XY:

0.114

AC XY:

15531

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.203

Gnomad AMR exome

AF:

0.0964

Gnomad ASJ exome

AF:

0.0787

Gnomad EAS exome

AF:

0.217

Gnomad SAS exome

AF:

0.0832

Gnomad FIN exome

AF:

0.0934

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.112

AC:

154022

AN:

1378432

Hom.:

9245

Cov.:

AF XY:

0.111

AC XY:

76914

AN XY:

690732

show subpopulations

Gnomad4 AFR exome

AF:

0.204

Gnomad4 AMR exome

AF:

0.0977

Gnomad4 ASJ exome

AF:

0.0804

Gnomad4 EAS exome

AF:

0.231

Gnomad4 SAS exome

AF:

0.0864

Gnomad4 FIN exome

AF:

0.0946

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.114

GnomAD4 genome

AF:

0.137

AC:

20835

AN:

152236

Hom.:

1585

Cov.:

AF XY:

0.135

AC XY:

10063

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.196

Gnomad4 AMR

AF:

0.110

Gnomad4 ASJ

AF:

0.0806

Gnomad4 EAS

AF:

0.233

Gnomad4 SAS

AF:

0.0899

Gnomad4 FIN

AF:

0.0889

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.126

Alfa

AF:

0.0790

Hom.:

145

Bravo

AF:

0.140

Asia WGS

AF:

0.175

AC:

607

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 25, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.0

DANN

Benign

0.51

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over