rs28377945

Variant summary

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

The NM_058246.4(DNAJB6):c.176-20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 1,612,064 control chromosomes in the GnomAD database, including 1,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 222 hom., cov: 33)

Exomes 𝑓: 0.039 ( 1273 hom. )

Consequence

DNAJB6
NM_058246.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.66

Variant links:

Genes affected

DNAJB6 (HGNC:14888): (DnaJ heat shock protein family (Hsp40) member B6) This gene encodes a member of the DNAJ protein family. DNAJ family members are characterized by a highly conserved amino acid stretch called the 'J-domain' and function as one of the two major classes of molecular chaperones involved in a wide range of cellular events, such as protein folding and oligomeric protein complex assembly. This family member may also play a role in polyglutamine aggregation in specific neurons. Alternative splicing of this gene results in multiple transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

DNAJB6 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=-0.82).

BP6

Variant 7-157366482-A-G is Benign according to our data. Variant chr7-157366482-A-G is described in ClinVar as [Benign]. Clinvar id is 262305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-157366482-A-G is described in Lovd as [Benign]. Variant chr7-157366482-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJB6	NM_058246.4 linkuse as main transcript	c.176-20A>G		intron_variant		ENST00000262177.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJB6	ENST00000262177.9 linkuse as main transcript	c.176-20A>G		intron_variant		1	NM_058246.4		O75190-1

Frequencies

GnomAD3 genomes

AF:

0.0494

AC:

7522

AN:

152152

Hom.:

220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0802

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.0320

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.0162

Gnomad SAS

AF:

0.0294

Gnomad FIN

AF:

0.0393

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0418

Gnomad OTH

AF:

0.0493

GnomAD3 exomes

AF:

0.0365

AC:

9154

AN:

251076

Hom.:

230

AF XY:

0.0361

AC XY:

4902

AN XY:

135694

show subpopulations

Gnomad AFR exome

AF:

0.0814

Gnomad AMR exome

AF:

0.0206

Gnomad ASJ exome

AF:

0.0153

Gnomad EAS exome

AF:

0.0145

Gnomad SAS exome

AF:

0.0307

Gnomad FIN exome

AF:

0.0425

Gnomad NFE exome

AF:

0.0405

Gnomad OTH exome

AF:

0.0395

GnomAD4 exome

AF:

0.0391

AC:

57150

AN:

1459794

Hom.:

1273

Cov.:

AF XY:

0.0387

AC XY:

28098

AN XY:

726308

show subpopulations

Gnomad4 AFR exome

AF:

0.0786

Gnomad4 AMR exome

AF:

0.0219

Gnomad4 ASJ exome

AF:

0.0141

Gnomad4 EAS exome

AF:

0.0112

Gnomad4 SAS exome

AF:

0.0301

Gnomad4 FIN exome

AF:

0.0430

Gnomad4 NFE exome

AF:

0.0409

Gnomad4 OTH exome

AF:

0.0377

GnomAD4 genome

AF:

0.0495

AC:

7532

AN:

152270

Hom.:

222

Cov.:

AF XY:

0.0483

AC XY:

3598

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0802

Gnomad4 AMR

AF:

0.0320

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.0162

Gnomad4 SAS

AF:

0.0288

Gnomad4 FIN

AF:

0.0393

Gnomad4 NFE

AF:

0.0418

Gnomad4 OTH

AF:

0.0488

Alfa

AF:

0.0415

Hom.:

Bravo

AF:

0.0493

Asia WGS

AF:

0.0340

AC:

119

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 29, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

Cadd

Benign

1.9

Dann

Benign

0.39

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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