15-34790024-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000558707.4(GJD2-DT):n.539C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 234,434 control chromosomes in the GnomAD database, including 8,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5236 hom., cov: 32)

Exomes 𝑓: 0.26 ( 2989 hom. )

Consequence

GJD2-DT
ENST00000558707.4 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.284

Publications

9 publications found

Variant links:

Genes affected

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

GJD2-DT links:

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 Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hypertrophic cardiomyopathy 11
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
atrial septal defect 5
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
dilated cardiomyopathy 1R
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
arthrogryposis syndrome
Inheritance: AD Classification: MODERATE Submitted by: University of Washington Center for Rare Disease Research (UW-CRDR)
dilated cardiomyopathy
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACTC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 15-34790024-C-T is Benign according to our data. Variant chr15-34790024-C-T is described in ClinVar as Benign. ClinVar VariationId is 315694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000558707.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GJD2-DT	NR_120329.1		n.299+12593C>T	intron	N/A
ACTC1	NM_005159.5	MANE Select	c.*388G>A	downstream_gene	N/A	NP_005150.1	P68032
ACTC1	NM_001406482.1		c.*388G>A	downstream_gene	N/A	NP_001393411.1	P68032

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
GJD2-DT	ENST00000558707.4	TSL:3	n.539C>T	non_coding_transcript_exon	Exon 3 of 3
GJD2-DT	ENST00000693120.3		n.378C>T	non_coding_transcript_exon	Exon 2 of 2
GJD2-DT	ENST00000713607.1		n.681C>T	non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38843

AN:

151992

Hom.:

5233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.459

Gnomad AMR

AF:

0.348

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.341

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.252

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.265

GnomAD4 exome

AF:

0.262

AC:

21536

AN:

82324

Hom.:

2989

Cov.:

AF XY:

0.266

AC XY:

11320

AN XY:

42608

show subpopulations

African (AFR)

AF:

0.162

AC:

563

AN:

3468

American (AMR)

AF:

0.347

AC:

1620

AN:

4674

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

530

AN:

2022

East Asian (EAS)

AF:

0.313

AC:

1680

AN:

5368

South Asian (SAS)

AF:

0.297

AC:

3025

AN:

10184

European-Finnish (FIN)

AF:

0.234

AC:

720

AN:

3078

Middle Eastern (MID)

AF:

0.270

AC:

AN:

296

European-Non Finnish (NFE)

AF:

0.250

AC:

12226

AN:

48840

Other (OTH)

AF:

0.249

AC:

1092

AN:

4394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

725

1449

2174

2898

3623

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

360

540

720

900

<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

AF:

0.255

AC:

38854

AN:

152110

Hom.:

5236

Cov.:

AF XY:

0.257

AC XY:

19110

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.169

AC:

7019

AN:

41486

American (AMR)

AF:

0.349

AC:

5330

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.267

AC:

928

AN:

3470

East Asian (EAS)

AF:

0.340

AC:

1763

AN:

5182

South Asian (SAS)

AF:

0.334

AC:

1607

AN:

4818

European-Finnish (FIN)

AF:

0.252

AC:

2666

AN:

10566

Middle Eastern (MID)

AF:

0.300

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.272

AC:

18475

AN:

67986

Other (OTH)

AF:

0.266

AC:

561

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1533

3066

4600

6133

7666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.264

Hom.:

16369

Bravo

AF:

0.258

Asia WGS

AF:

0.337

AC:

1171

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Dilated cardiomyopathy 1R (1)

Hypertrophic cardiomyopathy 11 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.1

(source)

DANN

Benign

0.75

PhyloP100

-0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over