2-217903858-G-A

Position:

• chr2-217903858-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387777.1(TNS1):​c.321+2477C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 479,394 control chromosomes in the GnomAD database, including 4,640 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 0.11 (1102 hom., cov: 33)
  • Exomes 𝑓: 0.14 (3538 hom.)
• Consequence: TNS1 NM_001387777.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.83

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNS1	NM_001387777.1	c.321+2477C>T		intron_variant		ENST00000682258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNS1	ENST00000682258.1	c.321+2477C>T		intron_variant			NM_001387777.1	P2

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16348 AN: 152072 Hom.: 1101 Cov.: 33

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.0776

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.138 AC: 45073 AN: 327204 Hom.: 3538 Cov.: 0 AF XY: 0.141 AC XY: 23799 AN XY: 168434

Gnomad4 AFR exome AF: 0.0447

Gnomad4 AMR exome AF: 0.0644

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.254

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.107 AC: 16346 AN: 152190 Hom.: 1102 Cov.: 33 AF XY: 0.111 AC XY: 8269 AN XY: 74410

Gnomad4 AFR AF: 0.0389

Gnomad4 AMR AF: 0.0775

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.103

Alfa AF: 0.128 Hom.: 1790

Bravo AF: 0.0978

Asia WGS AF: 0.244 AC: 845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.013
DANN	Benign	0.45

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: rs3791935; hg19: chr2-218768581;