15-34792014-C-G

Variant names:

• chr15-34792014-C-G
• rs3729755
• NM_005159.5:c.808+76G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005159.5(ACTC1):​c.808+76G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,525,606 control chromosomes in the GnomAD database, including 58,871 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5161 hom., cov: 33)
  • Exomes 𝑓: 0.28 (53710 hom.)
• Consequence: ACTC1 NM_005159.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.702

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 15-34792014-C-G is Benign according to our data. Variant chr15-34792014-C-G is described in ClinVar as [Benign]. Clinvar id is 1292062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-34792014-C-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTC1	NM_005159.5	c.808+76G>C		intron_variant	Intron 5 of 6	ENST00000290378.6	NP_005150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTC1	ENST00000290378.6	c.808+76G>C		intron_variant	Intron 5 of 6	1	NM_005159.5	ENSP00000290378.4

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38489 AN: 152018 Hom.: 5158 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.259

GnomAD4 exome AF: 0.276 AC: 379105 AN: 1373470 Hom.: 53710 Cov.: 20 AF XY: 0.278 AC XY: 190899 AN XY: 686918

Gnomad4 AFR exome AF: 0.159 AC: 5035 AN: 31608

Gnomad4 AMR exome AF: 0.376 AC: 16259 AN: 43198

Gnomad4 ASJ exome AF: 0.259 AC: 6572 AN: 25400

Gnomad4 EAS exome AF: 0.360 AC: 14033 AN: 39032

Gnomad4 SAS exome AF: 0.334 AC: 27859 AN: 83474

Gnomad4 FIN exome AF: 0.250 AC: 13074 AN: 52400

Gnomad4 NFE exome AF: 0.270 AC: 279815 AN: 1036838

Gnomad4 Remaining exome AF: 0.265 AC: 15234 AN: 57398

GnomAD4 genome AF: 0.253 AC: 38496 AN: 152136 Hom.: 5161 Cov.: 33 AF XY: 0.255 AC XY: 18940 AN XY: 74362

Gnomad4 AFR AF: 0.164 AC: 0.163593 AN: 0.163593

Gnomad4 AMR AF: 0.345 AC: 0.344972 AN: 0.344972

Gnomad4 ASJ AF: 0.256 AC: 0.256344 AN: 0.256344

Gnomad4 EAS AF: 0.342 AC: 0.341676 AN: 0.341676

Gnomad4 SAS AF: 0.334 AC: 0.334372 AN: 0.334372

Gnomad4 FIN AF: 0.252 AC: 0.251606 AN: 0.251606

Gnomad4 NFE AF: 0.271 AC: 0.27133 AN: 0.27133

Gnomad4 OTH AF: 0.259 AC: 0.259242 AN: 0.259242

Alfa AF: 0.249 Hom.: 604

Bravo AF: 0.255

Asia WGS AF: 0.334 AC: 1160 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.56
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

Publications

LitVar

Other links and lift over

dbSNP: rs3729755; hg19: chr15-35084215; COSMIC: COSV51761338; COSMIC: COSV51761338;