1-167430497-A-T

Variant names:

• chr1-167430497-A-T
• rs870875
• ENST00000700105.1:c.429+2527T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000700105.1(CD247):​c.429+2527T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD247 ENST00000700105.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.787
• Publications: 10 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000700105.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD247	NM_198053.3	MANE Select	c.*1184T>A		downstream_gene	N/A	NP_932170.1	P20963-1
	CD247	NM_001378515.1		c.*1184T>A		downstream_gene	N/A	NP_001365444.1
	CD247	NM_001378516.1		c.*1184T>A		downstream_gene	N/A	NP_001365445.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD247	ENST00000700105.1		c.429+2527T>A		intron	N/A	ENSP00000514800.1	A0A8V8TQY8
	CD247	ENST00000362089.10	TSL:1 MANE Select	c.*1184T>A		downstream_gene	N/A	ENSP00000354782.5	P20963-1
	CD247	ENST00000392122.4	TSL:1	c.*1184T>A		downstream_gene	N/A	ENSP00000375969.3	P20963-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 242674 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 123014

African (AFR) AF: 0.00 AC: 0 AN: 7122

American (AMR) AF: 0.00 AC: 0 AN: 7326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9158

East Asian (EAS) AF: 0.00 AC: 0 AN: 22736

South Asian (SAS) AF: 0.00 AC: 0 AN: 2158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20488

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1272

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 156230

Other (OTH) AF: 0.00 AC: 0 AN: 16184

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.46
DANN	Benign	0.80
PhyloP100		-0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs870875; hg19: chr1-167399734;