chr1-167484097-A-G

Variant names:

• chr1-167484097-A-G
• rs16859085
• NM_198053.3:c.58+34311T>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+34311T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,240 control chromosomes in the GnomAD database, including 2,503 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 0.17 (2503 hom., cov: 32)
• Consequence: CD247 NM_198053.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685
• 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: 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198053.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD247	NM_198053.3	MANE Select	c.58+34311T>C		intron	N/A	NP_932170.1
	CD247	NM_001378515.1		c.151+9867T>C		intron	N/A	NP_001365444.1
	CD247	NM_001378516.1		c.151+9867T>C		intron	N/A	NP_001365445.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD247	ENST00000362089.10	TSL:1 MANE Select	c.58+34311T>C		intron	N/A	ENSP00000354782.5
	CD247	ENST00000392122.4	TSL:1	c.58+34311T>C		intron	N/A	ENSP00000375969.3
	CD247	ENST00000700105.1		c.58+34311T>C		intron	N/A	ENSP00000514800.1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25958 AN: 152120 Hom.: 2501 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0841

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.171 AC: 25987 AN: 152240 Hom.: 2503 Cov.: 32 AF XY: 0.177 AC XY: 13197 AN XY: 74440

African (AFR) AF: 0.147 AC: 6107 AN: 41546

American (AMR) AF: 0.288 AC: 4399 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3472

East Asian (EAS) AF: 0.0839 AC: 434 AN: 5174

South Asian (SAS) AF: 0.260 AC: 1257 AN: 4826

European-Finnish (FIN) AF: 0.204 AC: 2164 AN: 10598

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10646 AN: 68006

Other (OTH) AF: 0.159 AC: 335 AN: 2112

Alfa AF: 0.159 Hom.: 9201

Bravo AF: 0.175

Asia WGS AF: 0.199 AC: 691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.66
PhyloP100		-0.69
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: rs16859085; hg19: chr1-167453334;