1-167492636-C-G

Variant names:

• chr1-167492636-C-G
• rs704848
• NM_198053.3:c.58+25772G>C

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+25772G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,032 control chromosomes in the GnomAD database, including 12,556 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 0.39 (12556 hom., cov: 31)
• Consequence: CD247 NM_198053.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD247	NM_198053.3	c.58+25772G>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+25772G>C		intron_variant	Intron 1 of 7	1	NM_198053.3	ENSP00000354782.5

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59734 AN: 151914 Hom.: 12559 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.393 AC: 59749 AN: 152032 Hom.: 12556 Cov.: 31 AF XY: 0.395 AC XY: 29325 AN XY: 74326

African (AFR) AF: 0.255 AC: 10593 AN: 41502

American (AMR) AF: 0.358 AC: 5475 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1608 AN: 3464

East Asian (EAS) AF: 0.638 AC: 3288 AN: 5152

South Asian (SAS) AF: 0.388 AC: 1868 AN: 4816

European-Finnish (FIN) AF: 0.472 AC: 4983 AN: 10554

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30461 AN: 67956

Other (OTH) AF: 0.429 AC: 905 AN: 2110

Alfa AF: 0.291 Hom.: 782

Bravo AF: 0.379

Asia WGS AF: 0.498 AC: 1731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.38
PhyloP100		0.10
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: rs704848; hg19: chr1-167461873;