11-1839720-G-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_003282.4(TNNI2):c.8+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000632 in 1,613,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000054 ( 0 hom. )
Consequence
TNNI2
NM_003282.4 intron
NM_003282.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.838
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 11-1839720-G-A is Benign according to our data. Variant chr11-1839720-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 511124.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 23 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNNI2 | NM_003282.4 | c.8+16G>A | intron_variant | ENST00000381911.6 | |||
TNNI2 | NM_001145829.2 | c.8+16G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNNI2 | ENST00000381911.6 | c.8+16G>A | intron_variant | 2 | NM_003282.4 | A1 | |||
TNNI2 | ENST00000252898.11 | c.8+16G>A | intron_variant | 3 | A1 | ||||
TNNI2 | ENST00000381906.5 | c.8+16G>A | intron_variant | 3 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152022Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250952Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135726
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GnomAD4 exome AF: 0.0000540 AC: 79AN: 1461678Hom.: 0 Cov.: 32 AF XY: 0.0000619 AC XY: 45AN XY: 727138
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GnomAD4 genome AF: 0.000151 AC: 23AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74384
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 31, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at