2-218029736-T-C

Position:

• chr2-218029736-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNS1	XM_047445637.1	c.156+4084A>G		intron_variant			XP_047301593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNS1	ENST00000649572.1	c.156+4084A>G		intron_variant				ENSP00000496807

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

Gnomad4 AFR AF: 0.978

Gnomad4 AMR AF: 0.932

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.880

Gnomad4 SAS AF: 0.861

Gnomad4 FIN AF: 0.839

Gnomad4 NFE AF: 0.869

Gnomad4 OTH AF: 0.912

Alfa AF: 0.896 Hom.: 14054

Bravo AF: 0.915

Asia WGS AF: 0.910 AC: 3164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2059741; hg19: chr2-218894459;