rs12133337

Positions:

• chr1-167483453-T-C

Variant summary

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

The NM_198053.3(CD247):​c.58+34955A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,086 control chromosomes in the GnomAD database, including 2,597 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 0.18 (2597 hom., cov: 32)
• Consequence: CD247 NM_198053.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD247	NM_198053.3	c.58+34955A>G		intron_variant		ENST00000362089.10	NP_932170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD247	ENST00000362089.10	c.58+34955A>G		intron_variant		1	NM_198053.3	ENSP00000354782	A1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26585 AN: 151966 Hom.: 2595 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.0852

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.175 AC: 26616 AN: 152086 Hom.: 2597 Cov.: 32 AF XY: 0.181 AC XY: 13468 AN XY: 74350

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.0848

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.163

Alfa AF: 0.178 Hom.: 399

Bravo AF: 0.180

Asia WGS AF: 0.202 AC: 700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.99
DANN	Benign	0.87

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: rs12133337; hg19: chr1-167452690;