2-217870230-A-G

Variant names:

• chr2-217870230-A-G
• rs10204348
• NM_001387777.1:c.1429+10668T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387777.1(TNS1):​c.1429+10668T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 152,106 control chromosomes in the GnomAD database, including 19,849 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 0.50 (19849 hom., cov: 33)
• Consequence: TNS1 NM_001387777.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 2 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387777.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNS1	NM_001387777.1	MANE Select	c.1429+10668T>C		intron	N/A	NP_001374706.1
	TNS1	NM_001438865.1		c.1492+10668T>C		intron	N/A	NP_001425794.1
	TNS1	NM_001438866.1		c.1429+10668T>C		intron	N/A	NP_001425795.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNS1	ENST00000682258.1	MANE Select	c.1429+10668T>C		intron	N/A	ENSP00000506917.1
	TNS1	ENST00000171887.8	TSL:1	c.1054+10668T>C		intron	N/A	ENSP00000171887.4
	TNS1	ENST00000419504.6	TSL:1	c.1054+10668T>C		intron	N/A	ENSP00000408724.1

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75285 AN: 151988 Hom.: 19835 Cov.: 33

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.495 AC: 75339 AN: 152106 Hom.: 19849 Cov.: 33 AF XY: 0.502 AC XY: 37319 AN XY: 74360

African (AFR) AF: 0.645 AC: 26762 AN: 41478

American (AMR) AF: 0.522 AC: 7979 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1714 AN: 3470

East Asian (EAS) AF: 0.689 AC: 3550 AN: 5156

South Asian (SAS) AF: 0.555 AC: 2674 AN: 4820

European-Finnish (FIN) AF: 0.427 AC: 4519 AN: 10594

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.388 AC: 26401 AN: 67988

Other (OTH) AF: 0.521 AC: 1100 AN: 2110

Alfa AF: 0.420 Hom.: 7245

Bravo AF: 0.511

Asia WGS AF: 0.600 AC: 2086 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.6
DANN	Benign	0.49
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10204348; hg19: chr2-218734953;