15-34790275-T-A

Variant names:

• chr15-34790275-T-A
• rs149031785
• NM_005159.5:c.*137A>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_005159.5(ACTC1):​c.*137A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000408 in 1,162,382 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (1 hom.)
• Consequence: ACTC1 NM_005159.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.10
• 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BP6: Variant 15-34790275-T-A is Benign according to our data. Variant chr15-34790275-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 885082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00184 (280/152276) while in subpopulation AFR AF = 0.0065 (270/41556). AF 95% confidence interval is 0.00586. There are 0 homozygotes in GnomAd4. There are 133 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 280 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.*137A>T		3_prime_UTR	Exon 7 of 7	NP_005150.1	P68032
	ACTC1	NM_001406482.1		c.*137A>T		3_prime_UTR	Exon 6 of 6	NP_001393411.1	P68032
	ACTC1	NM_001406483.1		c.*137A>T		3_prime_UTR	Exon 7 of 7	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.*137A>T		3_prime_UTR	Exon 7 of 7	ENSP00000290378.4	P68032
	ACTC1	ENST00000713613.1		c.*137A>T		3_prime_UTR	Exon 8 of 8	ENSP00000518909.1	A0AAQ5BGG2
	ACTC1	ENST00000868408.1		c.*137A>T		3_prime_UTR	Exon 7 of 7	ENSP00000538467.1

Frequencies

GnomAD3 genomes AF: 0.00184 AC: 280 AN: 152158 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000957

GnomAD4 exome AF: 0.000192 AC: 194 AN: 1010106 Hom.: 1 Cov.: 13 AF XY: 0.000164 AC XY: 85 AN XY: 518618

African (AFR) AF: 0.00632 AC: 154 AN: 24352

American (AMR) AF: 0.000419 AC: 17 AN: 40596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22662

East Asian (EAS) AF: 0.00 AC: 0 AN: 36474

South Asian (SAS) AF: 0.0000133 AC: 1 AN: 74952

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49780

Middle Eastern (MID) AF: 0.000310 AC: 1 AN: 3222

European-Non Finnish (NFE) AF: 0.00000281 AC: 2 AN: 712954

Other (OTH) AF: 0.000421 AC: 19 AN: 45114

GnomAD4 genome AF: 0.00184 AC: 280 AN: 152276 Hom.: 0 Cov.: 32 AF XY: 0.00179 AC XY: 133 AN XY: 74462

African (AFR) AF: 0.00650 AC: 270 AN: 41556

American (AMR) AF: 0.000458 AC: 7 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000278 Hom.: 0

Bravo AF: 0.00184

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Dilated cardiomyopathy 1R (1)
-	-	1	Hypertrophic cardiomyopathy 11 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	17
DANN	Benign	0.87
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism

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: rs149031785; hg19: chr15-35082476;