rs2056626

chr1-167451188-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198053.3(CD247):c.59-10421A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,910 control chromosomes in the GnomAD database, including 7,954 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (7954 hom., cov: 31)
• Consequence: CD247 NM_198053.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD247	NM_198053.3	c.59-10421A>C		intron_variant		ENST00000362089.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD247	ENST00000362089.10	c.59-10421A>C		intron_variant		1	NM_198053.3	A1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45318 AN: 151790 Hom.: 7959 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.298 AC: 45308 AN: 151910 Hom.: 7954 Cov.: 31 AF XY: 0.288 AC XY: 21384 AN XY: 74238

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.316

Alfa AF: 0.390 Hom.: 23522

Bravo AF: 0.292

Asia WGS AF: 0.174 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.29
Dann	Benign	0.52

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: rs2056626; hg19: chr1-167420425;