1-167442147-A-G

Variant names:

• chr1-167442147-A-G
• rs864537
• NM_198053.3:c.59-1380T>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.59-1380T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,136 control chromosomes in the GnomAD database, including 7,991 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 0.30 (7991 hom., cov: 32)
• Consequence: CD247 NM_198053.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.836
• Publications: 53 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD247	NM_198053.3	c.59-1380T>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.59-1380T>C		intron_variant	Intron 1 of 7	1	NM_198053.3	ENSP00000354782.5

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44908 AN: 152018 Hom.: 7994 Cov.: 32

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.334

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

GnomAD4 genome AF: 0.295 AC: 44890 AN: 152136 Hom.: 7991 Cov.: 32 AF XY: 0.290 AC XY: 21542 AN XY: 74346

African (AFR) AF: 0.0891 AC: 3702 AN: 41540

American (AMR) AF: 0.350 AC: 5347 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1691 AN: 3472

East Asian (EAS) AF: 0.206 AC: 1066 AN: 5172

South Asian (SAS) AF: 0.296 AC: 1427 AN: 4818

European-Finnish (FIN) AF: 0.274 AC: 2898 AN: 10588

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.406 AC: 27571 AN: 67954

Other (OTH) AF: 0.329 AC: 696 AN: 2114

Alfa AF: 0.370 Hom.: 53253

Bravo AF: 0.289

Asia WGS AF: 0.207 AC: 717 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.1
DANN	Benign	0.48
PhyloP100		0.84
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: rs864537; hg19: chr1-167411384; COSMIC: COSV62980460; COSMIC: COSV62980460;