rs704855

Positions:

• chr1-167500458-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_198053.3(CD247):​c.58+17950A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 152,352 control chromosomes in the GnomAD database, including 80 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 0.026 (80 hom., cov: 32)
• Consequence: CD247 NM_198053.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242

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=-0.81).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0265 (4034/152352) while in subpopulation NFE AF= 0.0359 (2442/68038). AF 95% confidence interval is 0.0347. There are 80 homozygotes in gnomad4. There are 2032 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 80 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD247	NM_198053.3	c.58+17950A>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+17950A>G		intron_variant		1	NM_198053.3	ENSP00000354782	A1

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 4034 AN: 152234 Hom.: 80 Cov.: 32

Gnomad AFR AF: 0.00634

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.0556

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.0728

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0359

Gnomad OTH AF: 0.0191

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

GnomAD4 genome AF: 0.0265 AC: 4034 AN: 152352 Hom.: 80 Cov.: 32 AF XY: 0.0273 AC XY: 2032 AN XY: 74516

Gnomad4 AFR AF: 0.00632

Gnomad4 AMR AF: 0.0153

Gnomad4 ASJ AF: 0.0556

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.0728

Gnomad4 NFE AF: 0.0359

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0305 Hom.: 12

Bravo AF: 0.0208

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.1
DANN	Benign	0.77

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: rs704855; hg19: chr1-167469695;