1-167431874-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_198053.3(CD247):c.430-128T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0216 in 811,836 control chromosomes in the GnomAD database, including 260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (32 hom., cov: 33)
  • Exomes 𝑓: 0.022 (228 hom.)
• Consequence: CD247 NM_198053.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0880

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-167431874-A-T is Benign according to our data. Variant chr1-167431874-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1203968.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0181 (2759/152310) while in subpopulation NFE AF= 0.0275 (1867/68010). AF 95% confidence interval is 0.0264. There are 32 homozygotes in gnomad4. There are 1322 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD247	NM_198053.3	c.430-128T>A		intron_variant		ENST00000362089.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD247	ENST00000362089.10	c.430-128T>A		intron_variant		1	NM_198053.3	A1

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2759 AN: 152192 Hom.: 32 Cov.: 33

Gnomad AFR AF: 0.00444

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0226

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0274

Gnomad OTH AF: 0.0273

GnomAD4 exome AF: 0.0223 AC: 14740 AN: 659526 Hom.: 228 AF XY: 0.0221 AC XY: 7832 AN XY: 354970

Gnomad4 AFR exome AF: 0.00538

Gnomad4 AMR exome AF: 0.0190

Gnomad4 ASJ exome AF: 0.0218

Gnomad4 EAS exome AF: 0.0000284

Gnomad4 SAS exome AF: 0.0126

Gnomad4 FIN exome AF: 0.0198

Gnomad4 NFE exome AF: 0.0275

Gnomad4 OTH exome AF: 0.0222

GnomAD4 genome AF: 0.0181 AC: 2759 AN: 152310 Hom.: 32 Cov.: 33 AF XY: 0.0177 AC XY: 1322 AN XY: 74482

Gnomad4 AFR AF: 0.00442

Gnomad4 AMR AF: 0.0226

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.0275

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0230 Hom.: 5

Asia WGS AF: 0.00751 AC: 27 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.68
Dann	Benign	0.83

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: rs189198029; hg19: chr1-167401111;