rs1214611

chr1-167479867-A-Gchr1-167479867-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198053.3(CD247):c.58+38541T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,052 control chromosomes in the GnomAD database, including 22,763 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 0.54 (22763 hom., cov: 33)
• Consequence: CD247 NM_198053.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD247	NM_198053.3	c.58+38541T>C		intron_variant		ENST00000362089.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD247	ENST00000362089.10	c.58+38541T>C		intron_variant		1	NM_198053.3	A1

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82410 AN: 151934 Hom.: 22748 Cov.: 33

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.542 AC: 82473 AN: 152052 Hom.: 22763 Cov.: 33 AF XY: 0.549 AC XY: 40820 AN XY: 74332

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.577

Alfa AF: 0.555 Hom.: 14073

Bravo AF: 0.543

Asia WGS AF: 0.657 AC: 2286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.026
Dann	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs1214611; hg19: chr1-167449104;