15-34794656-CG-CGG

Variant names:

• chr15-34794656-C-CG
• rs148433308
• NM_005159.5:c.129+23dupC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005159.5(ACTC1):​c.129+23dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00451 in 1,607,318 control chromosomes in the GnomAD database, including 308 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (161 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (147 hom.)
• Consequence: ACTC1 NM_005159.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.26
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 15-34794656-C-CG is Benign according to our data. Variant chr15-34794656-C-CG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 35646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0825 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005159.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTC1	NM_005159.5	MANE Select	c.129+23dupC		intron	N/A	NP_005150.1	P68032
	ACTC1	NM_001406482.1		c.129+23dupC		intron	N/A	NP_001393411.1	P68032
	ACTC1	NM_001406483.1		c.129+23dupC		intron	N/A	NP_001393412.1	P68032

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTC1	ENST00000290378.6	TSL:1 MANE Select	c.129+23_129+24insC		intron	N/A	ENSP00000290378.4	P68032
	ACTC1	ENST00000713613.1		c.129+23_129+24insC		intron	N/A	ENSP00000518909.1	A0AAQ5BGG2
	ACTC1	ENST00000868408.1		c.129+23_129+24insC		intron	N/A	ENSP00000538467.1

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3665 AN: 152152 Hom.: 159 Cov.: 32

Gnomad AFR AF: 0.0846

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.00593 AC: 1400 AN: 236080 AF XY: 0.00421

Gnomad AFR exome AF: 0.0896

Gnomad AMR exome AF: 0.00333

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00189

GnomAD4 exome AF: 0.00245 AC: 3559 AN: 1455048 Hom.: 147 Cov.: 31 AF XY: 0.00211 AC XY: 1529 AN XY: 723124

African (AFR) AF: 0.0844 AC: 2816 AN: 33380

American (AMR) AF: 0.00453 AC: 201 AN: 44354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25790

East Asian (EAS) AF: 0.00 AC: 0 AN: 39576

South Asian (SAS) AF: 0.000164 AC: 14 AN: 85558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52272

Middle Eastern (MID) AF: 0.00296 AC: 17 AN: 5752

European-Non Finnish (NFE) AF: 0.000153 AC: 170 AN: 1108292

Other (OTH) AF: 0.00568 AC: 341 AN: 60074

GnomAD4 genome AF: 0.0242 AC: 3685 AN: 152270 Hom.: 161 Cov.: 32 AF XY: 0.0226 AC XY: 1680 AN XY: 74466

African (AFR) AF: 0.0848 AC: 3524 AN: 41544

American (AMR) AF: 0.00693 AC: 106 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68014

Other (OTH) AF: 0.0166 AC: 35 AN: 2114

Alfa AF: 0.00124 Hom.: 0

Bravo AF: 0.0276

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs148433308; hg19: chr15-35086857;