rs1035672

chr2-217810476-G-Achr2-217810476-G-T

Variant summary

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

The NM_001387777.1(TNS1):c.5033-157C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 152,088 control chromosomes in the GnomAD database, including 31,990 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 0.64 (31990 hom., cov: 33)
• Consequence: TNS1 NM_001387777.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNS1	NM_001387777.1	c.5033-157C>T		intron_variant		ENST00000682258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNS1	ENST00000682258.1	c.5033-157C>T		intron_variant			NM_001387777.1	P2

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97503 AN: 151970 Hom.: 31939 Cov.: 33

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.642 AC: 97613 AN: 152088 Hom.: 31990 Cov.: 33 AF XY: 0.637 AC XY: 47357 AN XY: 74346

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.602

Gnomad4 OTH AF: 0.625

Alfa AF: 0.587 Hom.: 10549

Bravo AF: 0.657

Asia WGS AF: 0.518 AC: 1802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.8
Dann	Benign	0.37

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: rs1035672; hg19: chr2-218675199; COSMIC: COSV50730330; COSMIC: COSV50730330;