rs1035672

Variant names:

• chr2-217810476-G-A
• rs1035672
• NM_001387777.1:c.5033-157C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-217810476-G-A
• chr2-217810476-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 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.5033-157C>T		intron	N/A	NP_001374706.1
	TNS1	NM_001438865.1		c.5096-157C>T		intron	N/A	NP_001425794.1
	TNS1	NM_001438866.1		c.5030-157C>T		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.5033-157C>T		intron	N/A	ENSP00000506917.1
	TNS1	ENST00000171887.8	TSL:1	c.4721-157C>T		intron	N/A	ENSP00000171887.4
	TNS1	ENST00000419504.6	TSL:1	c.4679-157C>T		intron	N/A	ENSP00000408724.1

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

African (AFR) AF: 0.773 AC: 32063 AN: 41478

American (AMR) AF: 0.634 AC: 9693 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2326 AN: 3468

East Asian (EAS) AF: 0.507 AC: 2620 AN: 5166

South Asian (SAS) AF: 0.487 AC: 2343 AN: 4816

European-Finnish (FIN) AF: 0.535 AC: 5658 AN: 10580

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40913 AN: 67976

Other (OTH) AF: 0.625 AC: 1322 AN: 2114

Alfa AF: 0.590 Hom.: 12010

Bravo AF: 0.657

Asia WGS AF: 0.518 AC: 1802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.37
PhyloP100		-0.090
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: rs1035672; hg19: chr2-218675199; COSMIC: COSV50730330; COSMIC: COSV50730330;