15-34792014-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_005159.5(ACTC1):​c.808+76G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000436 in 1,375,326 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: ACTC1 NM_005159.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.702
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

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.808+76G>A		intron	N/A	NP_005150.1	P68032
	ACTC1	NM_001406482.1		c.808+76G>A		intron	N/A	NP_001393411.1	P68032
	ACTC1	NM_001406483.1		c.808+76G>A		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.808+76G>A		intron	N/A	ENSP00000290378.4	P68032
	ACTC1	ENST00000713613.1		c.919+76G>A		intron	N/A	ENSP00000518909.1	A0AAQ5BGG2
	ACTC1	ENST00000868408.1		c.814+76G>A		intron	N/A	ENSP00000538467.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000436 AC: 6 AN: 1375326 Hom.: 0 Cov.: 20 AF XY: 0.00000436 AC XY: 3 AN XY: 687768

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31634

American (AMR) AF: 0.00 AC: 0 AN: 43274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25430

East Asian (EAS) AF: 0.00 AC: 0 AN: 39054

South Asian (SAS) AF: 0.0000599 AC: 5 AN: 83520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4126

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1038354

Other (OTH) AF: 0.0000174 AC: 1 AN: 57490

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0190729), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.60
PhyloP100		-0.70

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: rs3729755; hg19: chr15-35084215;