rs185908824

chr11-1840957-C-Achr11-1840957-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003282.4(TNNI2):c.276+49C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000434 in 1,594,542 control chromosomes in the GnomAD database, including 6 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 0.0024 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (2 hom.)
• Consequence: TNNI2 NM_003282.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS2: High AC in GnomAd at 361 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNNI2	NM_003282.4	c.276+49C>A		intron_variant		ENST00000381911.6
TNNI2	NM_001145829.2	c.276+49C>A		intron_variant
TNNI2	NM_001145841.2	c.276+49C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNNI2	ENST00000381911.6	c.276+49C>A		intron_variant		2	NM_003282.4	A1
TNNI2	ENST00000252898.11	c.276+49C>A		intron_variant		3		A1
TNNI2	ENST00000381905.3	c.276+49C>A		intron_variant		3		P4
TNNI2	ENST00000381906.5	c.276+49C>A		intron_variant		3		A1

Frequencies

GnomAD3 genomes AF: 0.00237 AC: 361 AN: 152062 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00809

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000570 AC: 122 AN: 214188 Hom.: 1 AF XY: 0.000426 AC XY: 50 AN XY: 117396

Gnomad AFR exome AF: 0.00917

Gnomad AMR exome AF: 0.000288

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000216

Gnomad OTH exome AF: 0.000186

GnomAD4 exome AF: 0.000227 AC: 327 AN: 1442366 Hom.: 2 Cov.: 34 AF XY: 0.000221 AC XY: 158 AN XY: 716030

Gnomad4 AFR exome AF: 0.00752

Gnomad4 AMR exome AF: 0.000357

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000354

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000816

Gnomad4 OTH exome AF: 0.000874

GnomAD4 genome AF: 0.00240 AC: 365 AN: 152176 Hom.: 4 Cov.: 33 AF XY: 0.00223 AC XY: 166 AN XY: 74386

Gnomad4 AFR AF: 0.00816

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000144 Hom.: 0

Bravo AF: 0.00252

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.58
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs185908824; hg19: chr11-1862187;