rs45570832

Positions:

• chr1-201359580-G-A
• chr1-201359580-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.26

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]

ACMG classification

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	UniProt
TNNT2	NM_001276345.2	c.851+43C>T		intron_variant		ENST00000656932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNNT2	ENST00000656932.1	c.851+43C>T		intron_variant			NM_001276345.2	A2

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1536 AN: 152146 Hom.: 26 Cov.: 32

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.: 7 AF XY: 0.00186 AC XY: 212 AN XY: 114106

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.: 18 Cov.: 30 AF XY: 0.000896 AC XY: 632 AN XY: 705234

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.: 26 Cov.: 32 AF XY: 0.00967 AC XY: 720 AN XY: 74450

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.: 2

Bravo AF: 0.0117

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Other links and lift over

dbSNP: rs45570832; hg19: chr1-201328708;