dbSNP rs3791935: TNS1:c.321+2477C>T (chr2-217903858-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001387777.1(TNS1):c.321+2477C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 479,394 control chromosomes in the GnomAD database, including 4,640 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 0.11 ( 1102 hom., cov: 33)

Exomes 𝑓: 0.14 ( 3538 hom. )

Consequence

TNS1
NM_001387777.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.83

Publications

7 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNS1	NM_001387777.1 link	c.321+2477C>T		intron_variant	Intron 6 of 32	ENST00000682258.1	NP_001374706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNS1	ENST00000682258.1 link	c.321+2477C>T		intron_variant	Intron 6 of 32		NM_001387777.1	ENSP00000506917.1		Q9HBL0-3

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16348

AN:

152072

Hom.:

1101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0389

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.0776

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.279

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.103

GnomAD4 exome

AF:

0.138

AC:

45073

AN:

327204

Hom.:

3538

Cov.:

AF XY:

0.141

AC XY:

23799

AN XY:

168434

show subpopulations

African (AFR)

AF:

0.0447

AC:

415

AN:

9288

American (AMR)

AF:

0.0644

AC:

730

AN:

11332

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

1416

AN:

11038

East Asian (EAS)

AF:

0.224

AC:

5665

AN:

25234

South Asian (SAS)

AF:

0.254

AC:

4448

AN:

17524

European-Finnish (FIN)

AF:

0.133

AC:

3209

AN:

24124

Middle Eastern (MID)

AF:

0.193

AC:

315

AN:

1632

European-Non Finnish (NFE)

AF:

0.127

AC:

26209

AN:

206442

Other (OTH)

AF:

0.129

AC:

2666

AN:

20590

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1779

3558

5338

7117

8896

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

166

332

498

664

830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.107

AC:

16346

AN:

152190

Hom.:

1102

Cov.:

AF XY:

0.111

AC XY:

8269

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0389

AC:

1614

AN:

41544

American (AMR)

AF:

0.0775

AC:

1185

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

478

AN:

3470

East Asian (EAS)

AF:

0.232

AC:

1201

AN:

5176

South Asian (SAS)

AF:

0.279

AC:

1342

AN:

4806

European-Finnish (FIN)

AF:

0.129

AC:

1370

AN:

10586

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.128

AC:

8728

AN:

67996

Other (OTH)

AF:

0.103

AC:

218

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

734

1468

2202

2936

3670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.117

Hom.:

2271

Bravo

AF:

0.0978

Asia WGS

AF:

0.244

AC:

845

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.013

(source)

DANN

Benign

0.45

PhyloP100

-2.8

PromoterAI

-0.13

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over