rs2070664

Variant names:

• chr15-34793000-C-T
• rs2070664
• NM_005159.5:c.454+245G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-34793000-C-T
• chr15-34793000-C-A
• chr15-34793000-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005159.5(ACTC1):​c.454+245G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 568,658 control chromosomes in the GnomAD database, including 101,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). The gene ACTC1 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.62 (29715 hom., cov: 32)
  • Exomes 𝑓: 0.59 (72248 hom.)
• Consequence: ACTC1 NM_005159.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.56
• Publications: 14 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

Specifications for ACTC1 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-34793000-C-T is Benign according to our data. Variant chr15-34793000-C-T is described in ClinVar as Benign. ClinVar VariationId is 677956.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 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.454+245G>A		intron	N/A	NP_005150.1	P68032
	ACTC1	NM_001406482.1		c.454+245G>A		intron	N/A	NP_001393411.1	P68032
	ACTC1	NM_001406483.1		c.454+245G>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.454+245G>A		intron	N/A	ENSP00000290378.4	P68032
	ACTC1	ENST00000713613.1		c.565+245G>A		intron	N/A	ENSP00000518909.1	A0AAQ5BGG2
	ACTC1	ENST00000868408.1		c.454+245G>A		intron	N/A	ENSP00000538467.1

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94392 AN: 151846 Hom.: 29659 Cov.: 32

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.611

GnomAD4 exome AF: 0.586 AC: 244365 AN: 416694 Hom.: 72248 AF XY: 0.589 AC XY: 129414 AN XY: 219844

African (AFR) AF: 0.715 AC: 8401 AN: 11756

American (AMR) AF: 0.603 AC: 10523 AN: 17464

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 6848 AN: 12794

East Asian (EAS) AF: 0.547 AC: 15556 AN: 28430

South Asian (SAS) AF: 0.632 AC: 26998 AN: 42702

European-Finnish (FIN) AF: 0.502 AC: 13130 AN: 26176

Middle Eastern (MID) AF: 0.598 AC: 1095 AN: 1830

European-Non Finnish (NFE) AF: 0.588 AC: 147783 AN: 251512

Other (OTH) AF: 0.584 AC: 14031 AN: 24030

GnomAD4 genome AF: 0.622 AC: 94496 AN: 151964 Hom.: 29715 Cov.: 32 AF XY: 0.617 AC XY: 45834 AN XY: 74274

African (AFR) AF: 0.722 AC: 29916 AN: 41432

American (AMR) AF: 0.615 AC: 9388 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1864 AN: 3472

East Asian (EAS) AF: 0.538 AC: 2778 AN: 5160

South Asian (SAS) AF: 0.635 AC: 3054 AN: 4810

European-Finnish (FIN) AF: 0.503 AC: 5305 AN: 10546

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40105 AN: 67960

Other (OTH) AF: 0.616 AC: 1299 AN: 2110

Alfa AF: 0.595 Hom.: 31874

Bravo AF: 0.631

Asia WGS AF: 0.597 AC: 2073 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0090
DANN	Benign	0.66
PhyloP100		-3.6
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: rs2070664; hg19: chr15-35085201;