Variant rs45570832 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001276345.2(TNNT2):c.851+43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,572,922 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.010 ( 26 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 18 hom. )

Consequence

TNNT2
NM_001276345.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.26

Variant links:

Genes affected

TNNT2 (HGNC:11949): (troponin T2, cardiac type) This gene encodes the cardiac isoform of troponin T. The encoded protein is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration. Mutations in this gene have been associated with familial hypertrophic cardiomyopathy as well as with dilated cardiomyopathy. [provided by RefSeq, May 2022]

TNNT2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-201359580-G-A is Benign according to our data. Variant chr1-201359580-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 671447.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0101 (1540/152264) while in subpopulation AFR AF= 0.0343 (1422/41514). AF 95% confidence interval is 0.0328. There are 26 homozygotes in gnomad4. There are 720 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1540 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNNT2	NM_001276345.2 linkuse as main transcript	c.851+43C>T		intron_variant		ENST00000656932.1	NP_001263274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNNT2	ENST00000656932.1 linkuse as main transcript	c.851+43C>T		intron_variant			NM_001276345.2	ENSP00000499593	A2	P45379-1

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1536

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0342

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00240

AC:

513

AN:

213340

Hom.:

AF XY:

0.00186

AC XY:

212

AN XY:

114106

show subpopulations

Gnomad AFR exome

AF:

0.0345

Gnomad AMR exome

AF:

0.00178

Gnomad ASJ exome

AF:

0.000318

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000752

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000864

Gnomad OTH exome

AF:

0.00109

GnomAD4 exome

AF:

0.00108

AC:

1528

AN:

1420658

Hom.:

Cov.:

AF XY:

0.000896

AC XY:

632

AN XY:

705234

show subpopulations

Gnomad4 AFR exome

AF:

0.0342

Gnomad4 AMR exome

AF:

0.00215

Gnomad4 ASJ exome

AF:

0.000351

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000972

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000134

Gnomad4 OTH exome

AF:

0.00274

GnomAD4 genome

AF:

0.0101

AC:

1540

AN:

152264

Hom.:

Cov.:

AF XY:

0.00967

AC XY:

720

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0343

Gnomad4 AMR

AF:

0.00542

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00811

Hom.:

Bravo

AF:

0.0117

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.2

DANN

Benign

0.82

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over