Variant 15-34790143-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000560563.2(ACTC1):n.2303C>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 0.00726 in 419,096 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 64 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 12 hom. )

Consequence

ACTC1
ENST00000560563.2 non_coding_transcript_exon

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0340

Variant links:

Genes affected

GJD2-DT (HGNC:):

GJD2-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 15-34790143-G-A is Benign according to our data. Variant chr15-34790143-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 315697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GJD2-DT	NR_120329.1 linkuse as main transcript	n.299+12712G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL
GJD2-DT	ENST00000558707.3 linkuse as main transcript	n.616G>A	non_coding_transcript_exon_variant	3/3	3
ACTC1	ENST00000560563.2 linkuse as main transcript	n.2303C>T	non_coding_transcript_exon_variant	6/6	2
GJD2-DT	ENST00000693120.2 linkuse as main transcript	n.453G>A	non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2458

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0572

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00669

GnomAD4 exome

AF:

0.00215

AC:

575

AN:

266874

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

268

AN XY:

142006

show subpopulations

Gnomad4 AFR exome

AF:

0.0538

Gnomad4 AMR exome

AF:

0.00271

Gnomad4 ASJ exome

AF:

0.000127

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000275

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000204

Gnomad4 OTH exome

AF:

0.00310

GnomAD4 genome

AF:

0.0162

AC:

2467

AN:

152222

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1177

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0572

Gnomad4 AMR

AF:

0.00380

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.0136

Hom.:

Bravo

AF:

0.0178

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Dilated cardiomyopathy 1R

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Hypertrophic cardiomyopathy 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.2

DANN

Benign

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over