rs3754002

Positions:

• chr1-201425181-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000336092.8(TNNI1):​c.-74+1994G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,178 control chromosomes in the GnomAD database, including 19,160 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 0.46 (19160 hom., cov: 28)
• Consequence: TNNI1 ENST00000336092.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435

Genes affected

TNNI1 (HGNC:11945): (troponin I1, slow skeletal type) Troponin proteins associate with tropomyosin and regulate the calcium sensitivity of the myofibril contractile apparatus of striated muscles. Troponin I (TnI), along with troponin T (TnT) and troponin C (TnC), is one of 3 subunits that form the troponin complex of the thin filaments of striated muscle. TnI is the inhibitory subunit; blocking actin-myosin interactions and thereby mediating striated muscle relaxation. The TnI subfamily contains three genes: TnI-skeletal-fast-twitch, TnI-skeletal-slow-twitch, and TnI-cardiac. The TnI-fast and TnI-slow genes are expressed in fast-twitch and slow-twitch skeletal muscle fibers, respectively, while the TnI-cardiac gene is expressed exclusively in cardiac muscle tissue. This gene encodes the Troponin-I-skeletal-slow-twitch protein. This gene is expressed in cardiac and skeletal muscle during early development but is restricted to slow-twitch skeletal muscle fibers in adults. The encoded protein prevents muscle contraction by inhibiting calcium-mediated conformational changes in actin-myosin complexes. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.201425181C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNNI1	ENST00000336092.8	c.-74+1994G>A		intron_variant		5		ENSP00000337022.4

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69291 AN: 151064 Hom.: 19170 Cov.: 28

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.458 AC: 69274 AN: 151178 Hom.: 19160 Cov.: 28 AF XY: 0.451 AC XY: 33223 AN XY: 73652

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.638

Gnomad4 OTH AF: 0.474

Alfa AF: 0.487 Hom.: 3578

Bravo AF: 0.443

Asia WGS AF: 0.230 AC: 798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3754002; hg19: chr1-201394309;