chr2-217877279-G-A

Variant names:

• chr2-217877279-G-A
• rs4674220
• NM_001387777.1:c.1429+3619C>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.1429+3619C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 152,038 control chromosomes in the GnomAD database, including 33,752 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 0.65 (33752 hom., cov: 31)
• Consequence: TNS1 NM_001387777.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNS1	NM_001387777.1	c.1429+3619C>T		intron_variant	Intron 18 of 32	ENST00000682258.1	NP_001374706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNS1	ENST00000682258.1	c.1429+3619C>T		intron_variant	Intron 18 of 32		NM_001387777.1	ENSP00000506917.1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98729 AN: 151920 Hom.: 33725 Cov.: 31

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.650 AC: 98806 AN: 152038 Hom.: 33752 Cov.: 31 AF XY: 0.651 AC XY: 48349 AN XY: 74290

African (AFR) AF: 0.862 AC: 35775 AN: 41500

American (AMR) AF: 0.645 AC: 9855 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2366 AN: 3464

East Asian (EAS) AF: 0.710 AC: 3653 AN: 5148

South Asian (SAS) AF: 0.695 AC: 3345 AN: 4814

European-Finnish (FIN) AF: 0.483 AC: 5112 AN: 10576

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36414 AN: 67948

Other (OTH) AF: 0.673 AC: 1419 AN: 2110

Alfa AF: 0.581 Hom.: 20277

Bravo AF: 0.672

Asia WGS AF: 0.709 AC: 2464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.51
PhyloP100		-0.79
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: rs4674220; hg19: chr2-218742002;