2-217844492-T-C

Variant names:

• chr2-217844492-T-C
• rs929937
• NM_001387777.1:c.3007+3018A>G

Variant summary

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

The NM_001387777.1(TNS1):​c.3007+3018A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,922 control chromosomes in the GnomAD database, including 15,469 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 0.44 (15469 hom., cov: 32)
• Consequence: TNS1 NM_001387777.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 9 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]

ENSG00000305057 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNS1	NM_001387777.1	MANE Select	c.3007+3018A>G		intron	N/A	NP_001374706.1	Q9HBL0-3
	TNS1	NM_001438865.1		c.3070+3018A>G		intron	N/A	NP_001425794.1
	TNS1	NM_001438866.1		c.3007+3018A>G		intron	N/A	NP_001425795.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNS1	ENST00000682258.1	MANE Select	c.3007+3018A>G		intron	N/A	ENSP00000506917.1	Q9HBL0-3
	TNS1	ENST00000171887.8	TSL:1	c.2632+3018A>G		intron	N/A	ENSP00000171887.4	Q9HBL0-1
	TNS1	ENST00000419504.6	TSL:1	c.2632+3018A>G		intron	N/A	ENSP00000408724.1	E9PF55

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67081 AN: 151804 Hom.: 15454 Cov.: 32

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.442 AC: 67148 AN: 151922 Hom.: 15469 Cov.: 32 AF XY: 0.444 AC XY: 32980 AN XY: 74236

African (AFR) AF: 0.594 AC: 24620 AN: 41414

American (AMR) AF: 0.367 AC: 5616 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1555 AN: 3470

East Asian (EAS) AF: 0.349 AC: 1791 AN: 5138

South Asian (SAS) AF: 0.452 AC: 2177 AN: 4814

European-Finnish (FIN) AF: 0.405 AC: 4271 AN: 10558

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25585 AN: 67944

Other (OTH) AF: 0.442 AC: 929 AN: 2102

Alfa AF: 0.387 Hom.: 10080

Bravo AF: 0.441

Asia WGS AF: 0.414 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.97
DANN	Benign	0.38
PhyloP100		-1.8
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: rs929937; hg19: chr2-218709215; COSMIC: COSV50782400; COSMIC: COSV50782400;