7-157358540-C-T

Position:

chr7-157358540-C-T

Variant summary

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

The NM_058246.4(DNAJB6):c.-26-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 1,596,402 control chromosomes in the GnomAD database, including 262,231 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23231 hom., cov: 31)

Exomes 𝑓: 0.57 ( 239000 hom. )

Consequence

DNAJB6
NM_058246.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002081

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.543

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 7-157358540-C-T is Benign according to our data. Variant chr7-157358540-C-T is described in ClinVar as [Benign]. Clinvar id is 262304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJB6	NM_058246.4 linkuse as main transcript	c.-26-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000262177.9	NP_490647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJB6	ENST00000262177.9 linkuse as main transcript	c.-26-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_058246.4	ENSP00000262177		O75190-1

Frequencies

GnomAD3 genomes

AF:

0.548

AC:

83223

AN:

151798

Hom.:

23188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.454

Gnomad AMI

AF:

0.561

Gnomad AMR

AF:

0.598

Gnomad ASJ

AF:

0.499

Gnomad EAS

AF:

0.755

Gnomad SAS

AF:

0.532

Gnomad FIN

AF:

0.554

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.580

Gnomad OTH

AF:

0.572

GnomAD3 exomes

AF:

0.578

AC:

144571

AN:

250318

Hom.:

42310

AF XY:

0.575

AC XY:

77820

AN XY:

135326

show subpopulations

Gnomad AFR exome

AF:

0.454

Gnomad AMR exome

AF:

0.616

Gnomad ASJ exome

AF:

0.516

Gnomad EAS exome

AF:

0.773

Gnomad SAS exome

AF:

0.528

Gnomad FIN exome

AF:

0.553

Gnomad NFE exome

AF:

0.575

Gnomad OTH exome

AF:

0.579

GnomAD4 exome

AF:

0.573

AC:

827895

AN:

1444486

Hom.:

239000

Cov.:

AF XY:

0.572

AC XY:

411791

AN XY:

719720

show subpopulations

Gnomad4 AFR exome

AF:

0.454

Gnomad4 AMR exome

AF:

0.610

Gnomad4 ASJ exome

AF:

0.519

Gnomad4 EAS exome

AF:

0.748

Gnomad4 SAS exome

AF:

0.533

Gnomad4 FIN exome

AF:

0.548

Gnomad4 NFE exome

AF:

0.575

Gnomad4 OTH exome

AF:

0.568

GnomAD4 genome

AF:

0.548

AC:

83321

AN:

151916

Hom.:

23231

Cov.:

AF XY:

0.553

AC XY:

41038

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.455

Gnomad4 AMR

AF:

0.598

Gnomad4 ASJ

AF:

0.499

Gnomad4 EAS

AF:

0.755

Gnomad4 SAS

AF:

0.533

Gnomad4 FIN

AF:

0.554

Gnomad4 NFE

AF:

0.580

Gnomad4 OTH

AF:

0.575

Alfa

AF:

0.572

Hom.:

43419

Bravo

AF:

0.548

Asia WGS

AF:

0.612

AC:

2129

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 19, 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, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
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. -

Limb-Girdle Muscular Dystrophy, Dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.6

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.0

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