NM_001387777.1:c.4954+352C>T

Variant names:

• chr2-217812863-G-A
• rs76043829
• NM_001387777.1:c.4954+352C>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.4954+352C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0723 in 152,166 control chromosomes in the GnomAD database, including 509 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 0.072 (509 hom., cov: 32)
• Consequence: TNS1 NM_001387777.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.816
• Publications: 8 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNS1	NM_001387777.1	c.4954+352C>T		intron_variant	Intron 27 of 32	ENST00000682258.1	NP_001374706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNS1	ENST00000682258.1	c.4954+352C>T		intron_variant	Intron 27 of 32		NM_001387777.1	ENSP00000506917.1

Frequencies

GnomAD3 genomes AF: 0.0723 AC: 10993 AN: 152048 Hom.: 509 Cov.: 32

Gnomad AFR AF: 0.0347

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0517

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0236

Gnomad FIN AF: 0.0954

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0669

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

GnomAD4 genome AF: 0.0723 AC: 10995 AN: 152166 Hom.: 509 Cov.: 32 AF XY: 0.0706 AC XY: 5254 AN XY: 74396

African (AFR) AF: 0.0347 AC: 1441 AN: 41510

American (AMR) AF: 0.0517 AC: 791 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5158

South Asian (SAS) AF: 0.0234 AC: 113 AN: 4824

European-Finnish (FIN) AF: 0.0954 AC: 1012 AN: 10604

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6983 AN: 67990

Other (OTH) AF: 0.0658 AC: 139 AN: 2114

Alfa AF: 0.0701 Hom.: 237

Bravo AF: 0.0668

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.20
DANN	Benign	0.49
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs76043829; hg19: chr2-218677586;