2-218004665-A-G

Position:

• chr2-218004665-A-G

Variant summary

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

The ENST00000646520.1(TNS1):​c.96+5435T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 152,122 control chromosomes in the GnomAD database, including 36,212 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 0.68 (36212 hom., cov: 33)
• Consequence: TNS1 ENST00000646520.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNS1	XM_047445636.1	c.96+5435T>C		intron_variant
TNS1	XM_047445637.1	c.157-13609T>C		intron_variant
TNS1	XM_047445638.1	c.96+5435T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNS1	ENST00000646520.1	c.96+5435T>C		intron_variant				A2
TNS1	ENST00000649572.1	c.157-13609T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103400 AN: 152006 Hom.: 36198 Cov.: 33

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.680 AC: 103450 AN: 152122 Hom.: 36212 Cov.: 33 AF XY: 0.681 AC XY: 50670 AN XY: 74392

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.764

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.734

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.750

Gnomad4 OTH AF: 0.713

Alfa AF: 0.745 Hom.: 87873

Bravo AF: 0.682

Asia WGS AF: 0.699 AC: 2429 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	0.72
DANN	Benign	0.48

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs934036; hg19: chr2-218869388;