2-218029736-T-C

Variant names:

• chr2-218029736-T-C
• rs2059741
• ENST00000649572.1:c.156+4084A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000649572.1(TNS1):​c.156+4084A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 152,238 control chromosomes in the GnomAD database, including 62,442 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 0.90 (62442 hom., cov: 32)
• Consequence: TNS1 ENST00000649572.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 4 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000649572.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNS1	ENST00000649572.1		c.156+4084A>G		intron	N/A	ENSP00000496807.1	A0A3B3IRK7

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137509 AN: 152120 Hom.: 62383 Cov.: 32

Gnomad AFR AF: 0.978

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.931

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.910

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

GnomAD4 genome AF: 0.904 AC: 137628 AN: 152238 Hom.: 62442 Cov.: 32 AF XY: 0.903 AC XY: 67166 AN XY: 74418

African (AFR) AF: 0.978 AC: 40638 AN: 41550

American (AMR) AF: 0.932 AC: 14258 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3042 AN: 3472

East Asian (EAS) AF: 0.880 AC: 4554 AN: 5176

South Asian (SAS) AF: 0.861 AC: 4143 AN: 4814

European-Finnish (FIN) AF: 0.839 AC: 8892 AN: 10594

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 59085 AN: 68006

Other (OTH) AF: 0.912 AC: 1927 AN: 2114

Alfa AF: 0.892 Hom.: 23775

Bravo AF: 0.915

Asia WGS AF: 0.910 AC: 3164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.22
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs2059741; hg19: chr2-218894459;