rs1052231

Positions:

• chr1-167430837-T-A
• chr1-167430837-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.*844A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 398,660 control chromosomes in the GnomAD database, including 136,198 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 0.82 (51239 hom., cov: 35)
  • Exomes 𝑓: 0.83 (84959 hom.)
• Consequence: CD247 NM_198053.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180

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 (SAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD247	NM_198053.3	c.*844A>T		3_prime_UTR_variant	8/8	ENST00000362089.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD247	ENST00000362089.10	c.*844A>T		3_prime_UTR_variant	8/8	1	NM_198053.3	A1

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124589 AN: 152164 Hom.: 51196 Cov.: 35

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.860

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.839

GnomAD4 exome AF: 0.830 AC: 204472 AN: 246378 Hom.: 84959 Cov.: 0 AF XY: 0.830 AC XY: 103598 AN XY: 124840

Gnomad4 AFR exome AF: 0.758

Gnomad4 AMR exome AF: 0.864

Gnomad4 ASJ exome AF: 0.860

Gnomad4 EAS exome AF: 0.756

Gnomad4 SAS exome AF: 0.875

Gnomad4 FIN exome AF: 0.854

Gnomad4 NFE exome AF: 0.836

Gnomad4 OTH exome AF: 0.835

GnomAD4 genome AF: 0.819 AC: 124685 AN: 152282 Hom.: 51239 Cov.: 35 AF XY: 0.821 AC XY: 61127 AN XY: 74466

Gnomad4 AFR AF: 0.759

Gnomad4 AMR AF: 0.860

Gnomad4 ASJ AF: 0.857

Gnomad4 EAS AF: 0.765

Gnomad4 SAS AF: 0.869

Gnomad4 FIN AF: 0.860

Gnomad4 NFE AF: 0.836

Gnomad4 OTH AF: 0.840

Alfa AF: 0.826 Hom.: 6475

Bravo AF: 0.816

Asia WGS AF: 0.807 AC: 2806 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	0.35
DANN	Benign	0.59

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: rs1052231; hg19: chr1-167400074;