dbSNP rs148433308: ACTC1:c.129+23delC (chr15-34794656-CG-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_005159.5(ACTC1):c.129+23delC 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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.26

Publications

2 publications found

Variant links:

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]

ACTC1 links:

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

GJD2-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 1278145.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 69 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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000212

AC:

AN:

236080

AF XY:

0.00

show subpopulations

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000480

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000474

AC:

AN:

1455050

Hom.:

Cov.:

AF XY:

0.0000360

AC XY:

AN XY:

723122

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33380

American (AMR)

AF:

0.00

AC:

AN:

44354

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25790

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39576

South Asian (SAS)

AF:

0.0000234

AC:

AN:

85560

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52274

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.0000550

AC:

AN:

1108292

Other (OTH)

AF:

0.0000666

AC:

AN:

60072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over