7-157358329-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_058246.4(DNAJB6):c.-26-218C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 152,122 control chromosomes in the GnomAD database, including 233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.050 (233 hom., cov: 32)
• Consequence: DNAJB6 NM_058246.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.43

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-157358329-C-T is Benign according to our data. Variant chr7-157358329-C-T is described in ClinVar as [Benign]. Clinvar id is 679289.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.082 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJB6	NM_058246.4	c.-26-218C>T		intron_variant		ENST00000262177.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJB6	ENST00000262177.9	c.-26-218C>T		intron_variant		1	NM_058246.4

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7609 AN: 152004 Hom.: 228 Cov.: 32

Gnomad AFR AF: 0.0840

Gnomad AMI AF: 0.0582

Gnomad AMR AF: 0.0290

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.0395

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0415

Gnomad OTH AF: 0.0488

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0502 AC: 7630 AN: 152122 Hom.: 233 Cov.: 32 AF XY: 0.0491 AC XY: 3651 AN XY: 74388

Gnomad4 AFR AF: 0.0843

Gnomad4 AMR AF: 0.0290

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.0162

Gnomad4 SAS AF: 0.0288

Gnomad4 FIN AF: 0.0395

Gnomad4 NFE AF: 0.0415

Gnomad4 OTH AF: 0.0482

Alfa AF: 0.0464 Hom.: 25

Bravo AF: 0.0498

Asia WGS AF: 0.0380 AC: 131 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.35
Dann	Benign	0.68

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

Other links and lift over

dbSNP: rs58604246; hg19: chr7-157151023;