rs1737506

Variant names:

• chr1-167504188-A-T
• rs1737506
• NM_198053.3:c.58+14220T>A

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+14220T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,072 control chromosomes in the GnomAD database, including 5,317 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 0.24 (5317 hom., cov: 32)
• Consequence: CD247 NM_198053.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD247	NM_198053.3	c.58+14220T>A		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+14220T>A		intron_variant	Intron 1 of 7	1	NM_198053.3	ENSP00000354782.5

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36045 AN: 151954 Hom.: 5308 Cov.: 32

Gnomad AFR AF: 0.0879

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.0488

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.237 AC: 36059 AN: 152072 Hom.: 5317 Cov.: 32 AF XY: 0.238 AC XY: 17688 AN XY: 74322

African (AFR) AF: 0.0877 AC: 3641 AN: 41520

American (AMR) AF: 0.407 AC: 6228 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 630 AN: 3472

East Asian (EAS) AF: 0.0487 AC: 252 AN: 5176

South Asian (SAS) AF: 0.186 AC: 897 AN: 4818

European-Finnish (FIN) AF: 0.308 AC: 3247 AN: 10554

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20402 AN: 67932

Other (OTH) AF: 0.247 AC: 521 AN: 2110

Alfa AF: 0.265 Hom.: 734

Bravo AF: 0.239

Asia WGS AF: 0.139 AC: 484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.85
DANN	Benign	0.77
PhyloP100		0.41
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: rs1737506; hg19: chr1-167473425;