11-1840938-C-T

Variant names:

• chr11-1840938-C-T
• rs2271442
• NM_003282.4:c.276+30C>T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003282.4(TNNI2):​c.276+30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,602,912 control chromosomes in the GnomAD database, including 52,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3859 hom., cov: 33)
  • Exomes 𝑓: 0.26 (48784 hom.)
• Consequence: TNNI2 NM_003282.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.109

Genes affected

TNNI2 (HGNC:11946): (troponin I2, fast skeletal type) This gene encodes a fast-twitch skeletal muscle protein, a member of the troponin I gene family, and a component of the troponin complex including troponin T, troponin C and troponin I subunits. The troponin complex, along with tropomyosin, is responsible for the calcium-dependent regulation of striated muscle contraction. Mouse studies show that this component is also present in vascular smooth muscle and may play a role in regulation of smooth muscle function. In addition to muscle tissues, this protein is found in corneal epithelium, cartilage where it is an inhibitor of angiogenesis to inhibit tumor growth and metastasis, and mammary gland where it functions as a co-activator of estrogen receptor-related receptor alpha. This protein also suppresses tumor growth in human ovarian carcinoma. Mutations in this gene cause myopathy and distal arthrogryposis type 2B. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 11-1840938-C-T is Benign according to our data. Variant chr11-1840938-C-T is described in ClinVar as [Benign]. Clinvar id is 259023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-1840938-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNNI2	NM_003282.4	c.276+30C>T		intron_variant	Intron 6 of 7	ENST00000381911.6	NP_003273.1
TNNI2	NM_001145829.2	c.276+30C>T		intron_variant	Intron 6 of 7		NP_001139301.1
TNNI2	NM_001145841.2	c.276+30C>T		intron_variant	Intron 4 of 5		NP_001139313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNNI2	ENST00000381911.6	c.276+30C>T		intron_variant	Intron 6 of 7	2	NM_003282.4	ENSP00000371336.1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32116 AN: 151862 Hom.: 3857 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.170

GnomAD3 exomes AF: 0.248 AC: 56394 AN: 227494 Hom.: 7361 AF XY: 0.252 AC XY: 31315 AN XY: 124354

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.197

Gnomad ASJ exome AF: 0.170

Gnomad EAS exome AF: 0.260

Gnomad SAS exome AF: 0.263

Gnomad FIN exome AF: 0.359

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.255 AC: 370100 AN: 1450936 Hom.: 48784 Cov.: 37 AF XY: 0.256 AC XY: 184262 AN XY: 721096

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.242

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.211 AC: 32119 AN: 151976 Hom.: 3859 Cov.: 33 AF XY: 0.217 AC XY: 16125 AN XY: 74294

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.169

Alfa AF: 0.179 Hom.: 644

Bravo AF: 0.193

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.35		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.35		Position offset: -2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2271442; hg19: chr11-1862168;