Variant 11-1839074-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003282.4(TNNI2):c.-23+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,790 control chromosomes in the GnomAD database, including 2,005 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 1993 hom., cov: 32)

Exomes 𝑓: 0.15 ( 12 hom. )

Consequence

TNNI2
NM_003282.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.86

Variant links:

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]

TNNI2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 11-1839074-G-A is Benign according to our data. Variant chr11-1839074-G-A is described in ClinVar as [Benign]. Clinvar id is 1231135.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNNI2	NM_003282.4 linkuse as main transcript	c.-23+41G>A		intron_variant		ENST00000381911.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNNI2	ENST00000381911.6 linkuse as main transcript	c.-23+41G>A		intron_variant		2	NM_003282.4	A1	P48788-1

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21828

AN:

152006

Hom.:

1990

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0436

Gnomad AMI

AF:

0.160

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.0385

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.153

GnomAD4 exome

AF:

0.153

AC:

102

AN:

666

Hom.:

Cov.:

AF XY:

0.150

AC XY:

AN XY:

408

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.182

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.131

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.100

GnomAD4 genome

AF:

0.143

AC:

21825

AN:

152124

Hom.:

1993

Cov.:

AF XY:

0.145

AC XY:

10744

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0435

Gnomad4 AMR

AF:

0.199

Gnomad4 ASJ

AF:

0.139

Gnomad4 EAS

AF:

0.0386

Gnomad4 SAS

AF:

0.163

Gnomad4 FIN

AF:

0.202

Gnomad4 NFE

AF:

0.189

Gnomad4 OTH

AF:

0.152

Alfa

AF:

0.176

Hom.:

381

Bravo

AF:

0.139

Asia WGS

AF:

0.116

AC:

403

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.91

CADD

Benign

0.0020

DANN

Benign

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over