rs4774472

chr15-63061561-C-Achr15-63061561-C-Gchr15-63061561-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001018005.2(TPM1):c.564-152C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.808 in 840,410 control chromosomes in the GnomAD database, including 275,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.80 (48569 hom., cov: 31)
  • Exomes 𝑓: 0.81 (227098 hom.)
• Consequence: TPM1 NM_001018005.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0850

Genes affected

TPM1 (HGNC:12010): (tropomyosin 1) This gene is a member of the tropomyosin family of highly conserved, widely distributed actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. Tropomyosin is composed of two alpha-helical chains arranged as a coiled-coil. It is polymerized end to end along the two grooves of actin filaments and provides stability to the filaments. The encoded protein is one type of alpha helical chain that forms the predominant tropomyosin of striated muscle, where it also functions in association with the troponin complex to regulate the calcium-dependent interaction of actin and myosin during muscle contraction. In smooth muscle and non-muscle cells, alternatively spliced transcript variants encoding a range of isoforms have been described. Mutations in this gene are associated with type 3 familial hypertrophic cardiomyopathy and dilated cardiomyopathy 1Y. [provided by RefSeq, Jun 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-63061561-C-A is Benign according to our data. Variant chr15-63061561-C-A is described in ClinVar as [Benign]. Clinvar id is 1179789.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPM1	NM_001018005.2	c.564-152C>A		intron_variant		ENST00000403994.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPM1	ENST00000403994.9	c.564-152C>A		intron_variant		1	NM_001018005.2	A1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121113 AN: 152032 Hom.: 48513 Cov.: 31

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.787

GnomAD4 exome AF: 0.810 AC: 557820 AN: 688260 Hom.: 227098 Cov.: 9 AF XY: 0.812 AC XY: 297478 AN XY: 366574

Gnomad4 AFR exome AF: 0.756

Gnomad4 AMR exome AF: 0.885

Gnomad4 ASJ exome AF: 0.762

Gnomad4 EAS exome AF: 0.997

Gnomad4 SAS exome AF: 0.858

Gnomad4 FIN exome AF: 0.761

Gnomad4 NFE exome AF: 0.792

Gnomad4 OTH exome AF: 0.802

GnomAD4 genome AF: 0.797 AC: 121228 AN: 152150 Hom.: 48569 Cov.: 31 AF XY: 0.798 AC XY: 59329 AN XY: 74358

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.843

Gnomad4 ASJ AF: 0.759

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.876

Gnomad4 FIN AF: 0.756

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.788

Alfa AF: 0.791 Hom.: 5933

Bravo AF: 0.800

Asia WGS AF: 0.925 AC: 3216 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.73
Dann	Benign	0.37

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: rs4774472; hg19: chr15-63353760;