2-217844492-T-C

Position:

• chr2-217844492-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNS1	NM_001387777.1	c.3007+3018A>G		intron_variant		ENST00000682258.1	NP_001374706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNS1	ENST00000682258.1	c.3007+3018A>G		intron_variant			NM_001387777.1	ENSP00000506917.1

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

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.442

Alfa AF: 0.391 Hom.: 7370

Bravo AF: 0.441

Asia WGS AF: 0.414 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.97
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs929937; hg19: chr2-218709215; COSMIC: COSV50782400; COSMIC: COSV50782400;