rs45576635

chr1-201359577-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001276345.2(TNNT2):c.851+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 1,562,712 control chromosomes in the GnomAD database, including 708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.020 (46 hom., cov: 32)
  • Exomes 𝑓: 0.028 (662 hom.)
• Consequence: TNNT2 NM_001276345.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-201359577-G-A is Benign according to our data. Variant chr1-201359577-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0198 (3022/152306) while in subpopulation NFE AF= 0.0298 (2030/68020). AF 95% confidence interval is 0.0288. There are 46 homozygotes in gnomad4. There are 1334 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 3023 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNNT2	NM_001276345.2	c.851+46C>T		intron_variant		ENST00000656932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNNT2	ENST00000656932.1	c.851+46C>T		intron_variant			NM_001276345.2	A2

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 3023 AN: 152188 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.00553

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.00894

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0298

Gnomad OTH AF: 0.0272

GnomAD3 exomes AF: 0.0216 AC: 4550 AN: 211120 Hom.: 69 AF XY: 0.0224 AC XY: 2522 AN XY: 112732

Gnomad AFR exome AF: 0.00421

Gnomad AMR exome AF: 0.0177

Gnomad ASJ exome AF: 0.0340

Gnomad EAS exome AF: 0.0000623

Gnomad SAS exome AF: 0.0216

Gnomad FIN exome AF: 0.00965

Gnomad NFE exome AF: 0.0299

Gnomad OTH exome AF: 0.0265

GnomAD4 exome AF: 0.0280 AC: 39544 AN: 1410406 Hom.: 662 Cov.: 28 AF XY: 0.0280 AC XY: 19617 AN XY: 700346

Gnomad4 AFR exome AF: 0.00448

Gnomad4 AMR exome AF: 0.0187

Gnomad4 ASJ exome AF: 0.0343

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0208

Gnomad4 FIN exome AF: 0.0110

Gnomad4 NFE exome AF: 0.0314

Gnomad4 OTH exome AF: 0.0262

GnomAD4 genome AF: 0.0198 AC: 3022 AN: 152306 Hom.: 46 Cov.: 32 AF XY: 0.0179 AC XY: 1334 AN XY: 74478

Gnomad4 AFR AF: 0.00551

Gnomad4 AMR AF: 0.0247

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0205

Gnomad4 FIN AF: 0.00894

Gnomad4 NFE AF: 0.0298

Gnomad4 OTH AF: 0.0269

Alfa AF: 0.0261 Hom.: 14

Bravo AF: 0.0210

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.6
Dann	Benign	0.73

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: rs45576635; hg19: chr1-201328705;