Variant 2-217804450-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001387777.1(TNS1):c.*9C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,614,024 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0041 ( 29 hom. )

Consequence

TNS1
NM_001387777.1 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.90

Variant links:

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]

TNS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-217804450-G-A is Benign according to our data. Variant chr2-217804450-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3041622.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00409 (5978/1461750) while in subpopulation MID AF= 0.038 (219/5764). AF 95% confidence interval is 0.0339. There are 29 homozygotes in gnomad4_exome. There are 3054 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 507 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNS1	NM_001387777.1 linkuse as main transcript	c.*9C>T		3_prime_UTR_variant	33/33	ENST00000682258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNS1	ENST00000682258.1 linkuse as main transcript	c.*9C>T		3_prime_UTR_variant	33/33		NM_001387777.1	P2	Q9HBL0-3

Frequencies

GnomAD3 genomes

AF:

0.00335

AC:

509

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.00462

Gnomad OTH

AF:

0.00812

GnomAD3 exomes

AF:

0.00390

AC:

980

AN:

251310

Hom.:

AF XY:

0.00418

AC XY:

568

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00460

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00451

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.00442

Gnomad OTH exome

AF:

0.00604

GnomAD4 exome

AF:

0.00409

AC:

5978

AN:

1461750

Hom.:

Cov.:

AF XY:

0.00420

AC XY:

3054

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00179

Gnomad4 AMR exome

AF:

0.00485

Gnomad4 ASJ exome

AF:

0.0111

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00467

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00395

Gnomad4 OTH exome

AF:

0.00631

GnomAD4 genome

AF:

0.00333

AC:

507

AN:

152274

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

231

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00496

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00462

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.00358

Hom.:

Bravo

AF:

0.00361

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

TNS1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 01, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

8.1

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over