ENST00000470379.2:c.-156G>A

Variant names:

• chr1-167439433-C-T
• rs840016
• ENST00000470379.2:c.-156G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000470379.2(CD247):​c.-156G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,610,448 control chromosomes in the GnomAD database, including 114,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (7494 hom., cov: 33)
  • Exomes 𝑓: 0.37 (107218 hom.)
• Consequence: CD247 ENST00000470379.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.535
• Publications: 35 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-167439433-C-T is Benign according to our data. Variant chr1-167439433-C-T is described in ClinVar as Benign. ClinVar VariationId is 1179252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000470379.2. 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.163-33G>A		intron	N/A	NP_932170.1	P20963-1
	CD247	NM_001378515.1		c.256-33G>A		intron	N/A	NP_001365444.1
	CD247	NM_001378516.1		c.256-33G>A		intron	N/A	NP_001365445.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD247	ENST00000470379.2	TSL:1	c.-156G>A		5_prime_UTR	Exon 1 of 6	ENSP00000514807.1	A0A8V8TPQ0
	CD247	ENST00000362089.10	TSL:1 MANE Select	c.163-33G>A		intron	N/A	ENSP00000354782.5	P20963-1
	CD247	ENST00000392122.4	TSL:1	c.163-33G>A		intron	N/A	ENSP00000375969.3	P20963-3

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43010 AN: 152132 Hom.: 7499 Cov.: 33

Gnomad AFR AF: 0.0879

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.325

GnomAD2 exomes AF: 0.311 AC: 77777 AN: 250192 AF XY: 0.323

Gnomad AFR exome AF: 0.0805

Gnomad AMR exome AF: 0.236

Gnomad ASJ exome AF: 0.482

Gnomad EAS exome AF: 0.105

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.399

Gnomad OTH exome AF: 0.358

GnomAD4 exome AF: 0.373 AC: 543787 AN: 1458198 Hom.: 107218 Cov.: 31 AF XY: 0.373 AC XY: 270325 AN XY: 725622

African (AFR) AF: 0.0774 AC: 2587 AN: 33426

American (AMR) AF: 0.240 AC: 10741 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 12465 AN: 26102

East Asian (EAS) AF: 0.101 AC: 3988 AN: 39678

South Asian (SAS) AF: 0.301 AC: 25915 AN: 86152

European-Finnish (FIN) AF: 0.253 AC: 13495 AN: 53388

Middle Eastern (MID) AF: 0.476 AC: 2742 AN: 5764

European-Non Finnish (NFE) AF: 0.406 AC: 449986 AN: 1108744

Other (OTH) AF: 0.363 AC: 21868 AN: 60244

GnomAD4 genome AF: 0.282 AC: 42994 AN: 152250 Hom.: 7494 Cov.: 33 AF XY: 0.274 AC XY: 20367 AN XY: 74432

African (AFR) AF: 0.0877 AC: 3643 AN: 41558

American (AMR) AF: 0.306 AC: 4684 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1693 AN: 3472

East Asian (EAS) AF: 0.105 AC: 543 AN: 5170

South Asian (SAS) AF: 0.292 AC: 1410 AN: 4830

European-Finnish (FIN) AF: 0.230 AC: 2444 AN: 10614

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27409 AN: 67986

Other (OTH) AF: 0.321 AC: 678 AN: 2114

Alfa AF: 0.350 Hom.: 23448

Bravo AF: 0.276

Asia WGS AF: 0.163 AC: 563 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	10
DANN	Benign	0.91
PhyloP100		0.54
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: rs840016; hg19: chr1-167408670; COSMIC: COSV62980812; COSMIC: COSV62980812;