rs76043829

chr2-217812863-G-A

Variant summary

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

The NM_001387777.1(TNS1):c.4954+352C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 152,166 control chromosomes in the GnomAD database, including 509 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 0.072 (509 hom., cov: 32)
• Consequence: TNS1 NM_001387777.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.816

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNS1	NM_001387777.1	c.4954+352C>T		intron_variant		ENST00000682258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNS1	ENST00000682258.1	c.4954+352C>T		intron_variant			NM_001387777.1	P2

Frequencies

GnomAD3 genomes AF: 0.0723 AC: 10993 AN: 152048 Hom.: 509 Cov.: 32

Gnomad AFR AF: 0.0347

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0517

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.0954

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0669

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

GnomAD4 genome AF: 0.0723 AC: 10995 AN: 152166 Hom.: 509 Cov.: 32 AF XY: 0.0706 AC XY: 5254 AN XY: 74396

Gnomad4 AFR AF: 0.0347

Gnomad4 AMR AF: 0.0517

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0234

Gnomad4 FIN AF: 0.0954

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0658

Alfa AF: 0.0850 Hom.: 78

Bravo AF: 0.0668

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.20
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs76043829; hg19: chr2-218677586;