7-157337288-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.-27+144C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,208 control chromosomes in the GnomAD database, including 22,857 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.55 (22856 hom., cov: 31)
  • Exomes 𝑓: 0.16 (1 hom.)
• Consequence: DNAJB6 NM_058246.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.767

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=-0.87).
• BP6: Variant 7-157337288-C-T is Benign according to our data. Variant chr7-157337288-C-T is described in ClinVar as [Benign]. Clinvar id is 1293058.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJB6	NM_058246.4	c.-27+144C>T		intron_variant		ENST00000262177.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJB6	ENST00000262177.9	c.-27+144C>T		intron_variant		1	NM_058246.4

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82444 AN: 151026 Hom.: 22819 Cov.: 31

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.638

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.574

GnomAD4 exome AF: 0.158 AC: 12 AN: 76 Hom.: 1 AF XY: 0.204 AC XY: 11 AN XY: 54

Gnomad4 AFR exome AF: 0.500

Gnomad4 SAS exome AF: 0.231

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.546 AC: 82529 AN: 151132 Hom.: 22856 Cov.: 31 AF XY: 0.551 AC XY: 40670 AN XY: 73872

Gnomad4 AFR AF: 0.452

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.756

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.577

Alfa AF: 0.525 Hom.: 1593

Bravo AF: 0.546

Asia WGS AF: 0.608 AC: 2080 AN: 3424

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

Jul 03, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.7
Dann	Benign	0.97

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: rs9297107; hg19: chr7-157129982;