rs858543

Variant names:

• chr1-167498061-A-G
• rs858543
• NM_198053.3:c.58+20347T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-167498061-A-G
• chr1-167498061-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198053.3(CD247):​c.58+20347T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 152,074 control chromosomes in the GnomAD database, including 41,586 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 0.74 (41586 hom., cov: 31)
• Consequence: CD247 NM_198053.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.571
• Publications: 9 publications found

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]

CD247 Gene-Disease associations (from GenCC):

• immunodeficiency 25

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD247	NM_198053.3	c.58+20347T>C		intron_variant	Intron 1 of 7	ENST00000362089.10	NP_932170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD247	ENST00000362089.10	c.58+20347T>C		intron_variant	Intron 1 of 7	1	NM_198053.3	ENSP00000354782.5

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112095 AN: 151954 Hom.: 41543 Cov.: 31

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.738 AC: 112188 AN: 152074 Hom.: 41586 Cov.: 31 AF XY: 0.736 AC XY: 54694 AN XY: 74324

African (AFR) AF: 0.764 AC: 31700 AN: 41472

American (AMR) AF: 0.752 AC: 11503 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2428 AN: 3470

East Asian (EAS) AF: 0.495 AC: 2554 AN: 5160

South Asian (SAS) AF: 0.739 AC: 3557 AN: 4814

European-Finnish (FIN) AF: 0.746 AC: 7899 AN: 10584

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.741 AC: 50354 AN: 67966

Other (OTH) AF: 0.718 AC: 1520 AN: 2116

Alfa AF: 0.734 Hom.: 63513

Bravo AF: 0.734

Asia WGS AF: 0.619 AC: 2155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.70
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs858543; hg19: chr1-167467298;