chr11-1839194-G-C

Position:

• chr11-1839194-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003282.4(TNNI2):​c.-23+161G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,144 control chromosomes in the GnomAD database, including 2,626 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.17 (2626 hom., cov: 32)
• Consequence: TNNI2 NM_003282.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.39

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-1839194-G-C is Benign according to our data. Variant chr11-1839194-G-C is described in ClinVar as [Benign]. Clinvar id is 1228964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNNI2	NM_003282.4	c.-23+161G>C		intron_variant		ENST00000381911.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNNI2	ENST00000381911.6	c.-23+161G>C		intron_variant		2	NM_003282.4	A1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25219 AN: 152026 Hom.: 2628 Cov.: 32

Gnomad AFR AF: 0.0528

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.0950

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.144

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.166 AC: 25218 AN: 152144 Hom.: 2626 Cov.: 32 AF XY: 0.165 AC XY: 12268 AN XY: 74374

Gnomad4 AFR AF: 0.0527

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.0950

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.143

Alfa AF: 0.0768 Hom.: 136

Bravo AF: 0.157

Asia WGS AF: 0.180 AC: 630 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 19, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.4
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs75695272; hg19: chr11-1860424;