rs1052230

Positions:

• chr1-167430844-G-C

Variant summary

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

The NM_198053.3(CD247):​c.*837C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 398,696 control chromosomes in the GnomAD database, including 4,578 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 0.15 (1703 hom., cov: 33)
  • Exomes 𝑓: 0.15 (2875 hom.)
• Consequence: CD247 NM_198053.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD247	NM_198053.3	c.*837C>G		3_prime_UTR_variant	8/8	ENST00000362089.10	NP_932170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD247	ENST00000362089	c.*837C>G		3_prime_UTR_variant	8/8	1	NM_198053.3	ENSP00000354782.5

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22153 AN: 152144 Hom.: 1701 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.149 AC: 36775 AN: 246434 Hom.: 2875 Cov.: 0 AF XY: 0.150 AC XY: 18688 AN XY: 124860

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.244

Gnomad4 SAS exome AF: 0.0986

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.146 AC: 22162 AN: 152262 Hom.: 1703 Cov.: 33 AF XY: 0.144 AC XY: 10715 AN XY: 74440

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.135

Alfa AF: 0.142 Hom.: 214

Bravo AF: 0.146

Asia WGS AF: 0.181 AC: 629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.19
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1052230; hg19: chr1-167400081;