chr1-201425181-C-T

Variant names:

• chr1-201425181-C-T
• rs3754002
• ENST00000336092.8:c.-74+1994G>A

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]

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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNNI1	ENST00000336092.8	c.-74+1994G>A		intron_variant	Intron 3 of 11	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;