1-167432017-C-T

Position:

• chr1-167432017-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198053.3(CD247):​c.430-271G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,214 control chromosomes in the GnomAD database, including 1,231 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1231 hom., cov: 33)
• Consequence: CD247 NM_198053.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.927

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 1-167432017-C-T is Benign according to our data. Variant chr1-167432017-C-T is described in ClinVar as [Benign]. Clinvar id is 1266856.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD247	NM_198053.3	c.430-271G>A		intron_variant		ENST00000362089.10	NP_932170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD247	ENST00000362089.10	c.430-271G>A		intron_variant		1	NM_198053.3	ENSP00000354782	A1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16048 AN: 152096 Hom.: 1229 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0506

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0507

Gnomad OTH AF: 0.103

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.106 AC: 16082 AN: 152214 Hom.: 1231 Cov.: 33 AF XY: 0.108 AC XY: 8054 AN XY: 74398

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.0506

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.0507

Gnomad4 OTH AF: 0.107

Alfa AF: 0.0579 Hom.: 479

Bravo AF: 0.105

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.8
DANN	Benign	0.41

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: rs16859030; hg19: chr1-167401254;