rs3791950

chr2-217865142-C-A

Variant summary

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

The NM_001387777.1(TNS1):c.1429+15756G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 151,798 control chromosomes in the GnomAD database, including 34,230 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 0.65 (34230 hom., cov: 31)
• Consequence: TNS1 NM_001387777.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26

Genes affected

TNS1 (HGNC:11973): (tensin 1) The protein encoded by this gene localizes to focal adhesions, regions of the plasma membrane where the cell attaches to the extracellular matrix. This protein crosslinks actin filaments and contains a Src homology 2 (SH2) domain, which is often found in molecules involved in signal transduction. This protein is a substrate of calpain II. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNS1	NM_001387777.1	c.1429+15756G>T		intron_variant		ENST00000682258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNS1	ENST00000682258.1	c.1429+15756G>T		intron_variant			NM_001387777.1	P2

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99131 AN: 151680 Hom.: 34204 Cov.: 31

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.654 AC: 99207 AN: 151798 Hom.: 34230 Cov.: 31 AF XY: 0.654 AC XY: 48462 AN XY: 74154

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.672

Gnomad4 EAS AF: 0.710

Gnomad4 SAS AF: 0.691

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.676

Alfa AF: 0.561 Hom.: 19523

Bravo AF: 0.676

Asia WGS AF: 0.701 AC: 2437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.25
Dann	Benign	0.26

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: rs3791950; hg19: chr2-218729865;