chr1-167485121-T-C

Variant names:

• chr1-167485121-T-C
• rs858556
• NM_198053.3:c.58+33287A>G

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+33287A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 152,140 control chromosomes in the GnomAD database, including 10,236 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 0.35 (10236 hom., cov: 33)
• Consequence: CD247 NM_198053.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD247	NM_198053.3	c.58+33287A>G		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+33287A>G		intron_variant	Intron 1 of 7	1	NM_198053.3	ENSP00000354782.5

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53906 AN: 152022 Hom.: 10227 Cov.: 33

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.373

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.355 AC: 53942 AN: 152140 Hom.: 10236 Cov.: 33 AF XY: 0.354 AC XY: 26318 AN XY: 74358

African (AFR) AF: 0.244 AC: 10118 AN: 41518

American (AMR) AF: 0.476 AC: 7289 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.373 AC: 1292 AN: 3466

East Asian (EAS) AF: 0.135 AC: 698 AN: 5174

South Asian (SAS) AF: 0.412 AC: 1989 AN: 4824

European-Finnish (FIN) AF: 0.336 AC: 3552 AN: 10566

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27740 AN: 67976

Other (OTH) AF: 0.362 AC: 766 AN: 2114

Alfa AF: 0.360 Hom.: 1284

Bravo AF: 0.360

Asia WGS AF: 0.312 AC: 1083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.18
DANN	Benign	0.45
PhyloP100		-2.6
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: rs858556; hg19: chr1-167454358;