rs148433308

chr15-34794656-CG-Cchr15-34794656-CG-CGGchr15-34794656-CG-CGGGchr15-34794656-CG-CGGGGGG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_005159.5(ACTC1):c.129+23del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000474 in 1,455,050 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: ACTC1 NM_005159.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.26

Genes affected

ACTC1 (HGNC:143): (actin alpha cardiac muscle 1) Actins are highly conserved proteins that are involved in various types of cell motility. Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to four others. The protein encoded by this gene belongs to the actin family which is comprised of three main groups of actin isoforms, alpha, beta, and gamma. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. Defects in this gene have been associated with idiopathic dilated cardiomyopathy (IDC) and familial hypertrophic cardiomyopathy (FHC). [provided by RefSeq, Jul 2008]

GJD2-DT (HGNC:55560): (GJD2 divergent transcript)

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 15-34794656-CG-C is Benign according to our data. Variant chr15-34794656-CG-C is described in ClinVar as [Benign]. Clinvar id is 1278145.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-34794656-CG-C is described in Lovd as [Likely_benign]. Variant chr15-34794656-CG-C is described in Lovd as [Benign].
• BS2: High AC in GnomAdExome at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTC1	NM_005159.5	c.129+23del		intron_variant		ENST00000290378.6
GJD2-DT	NR_120329.1	n.300-15834del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTC1	ENST00000290378.6	c.129+23del		intron_variant		1	NM_005159.5	P1
GJD2-DT	ENST00000671663.1	n.95-15834del		intron_variant, non_coding_transcript_variant
GJD2-DT	ENST00000503496.6	n.300-15834del		intron_variant, non_coding_transcript_variant		2
ACTC1	ENST00000560563.2	n.235+23del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000212 AC: 5 AN: 236080 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 129356

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000480

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000474 AC: 69 AN: 1455050 Hom.: 0 Cov.: 31 AF XY: 0.0000360 AC XY: 26 AN XY: 723122

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0000234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000550

Gnomad4 OTH exome AF: 0.0000666

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

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

- -

Computational scores

Source: dbNSFP v4.3

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: rs148433308; hg19: chr15-35086857;