rs8109288

Positions:

• chr19-16074749-G-A

Variant summary

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

The ENST00000624324.2(ENSG00000279198):​n.2647C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0375 in 152,286 control chromosomes in the GnomAD database, including 191 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 0.038 (191 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENST00000624324.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.317

Genes affected

(HGNC:):

TPM4 (HGNC:12013): (tropomyosin 4) This gene encodes a member of the tropomyosin family of actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. Tropomyosins are dimers of coiled-coil proteins that polymerize end-to-end along the major groove in most actin filaments. They provide stability to the filaments and regulate access of other actin-binding proteins. In muscle cells, they regulate muscle contraction by controlling the binding of myosin heads to the actin filament. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2009]

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 (AFR) allele frequency at 95% confidence interval = 0.0898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPM4	NM_001145160.2	c.115-1298G>A		intron_variant			NP_001138632.1
TPM4	NM_001367836.1	c.67-1298G>A		intron_variant			NP_001354765.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000624324.2	n.2647C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5710 AN: 152168 Hom.: 192 Cov.: 32

Gnomad AFR AF: 0.0923

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0195

Gnomad ASJ AF: 0.00808

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00993

Gnomad FIN AF: 0.00527

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0201

Gnomad OTH AF: 0.0359

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 96 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 54

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0375 AC: 5717 AN: 152286 Hom.: 191 Cov.: 32 AF XY: 0.0356 AC XY: 2652 AN XY: 74470

Gnomad4 AFR AF: 0.0923

Gnomad4 AMR AF: 0.0194

Gnomad4 ASJ AF: 0.00808

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00994

Gnomad4 FIN AF: 0.00527

Gnomad4 NFE AF: 0.0201

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0233 Hom.: 66

Bravo AF: 0.0410

Asia WGS AF: 0.0110 AC: 40 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	1.7
DANN	Benign	0.53

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

Other links and lift over

dbSNP: rs8109288; hg19: chr19-16185559;