7-157337335-A-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+191A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 149,858 control chromosomes in the GnomAD database, including 39,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.72 (39063 hom., cov: 28)
• Consequence: DNAJB6 NM_058246.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.343

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=-0.94).
• BP6: Variant 7-157337335-A-T is Benign according to our data. Variant chr7-157337335-A-T is described in ClinVar as [Benign]. Clinvar id is 1224222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJB6	NM_058246.4	c.-27+191A>T		intron_variant		ENST00000262177.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJB6	ENST00000262177.9	c.-27+191A>T		intron_variant		1	NM_058246.4

Frequencies

GnomAD3 genomes AF: 0.715 AC: 107114 AN: 149752 Hom.: 39006 Cov.: 28

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.710

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

GnomAD4 genome AF: 0.716 AC: 107226 AN: 149858 Hom.: 39063 Cov.: 28 AF XY: 0.713 AC XY: 52116 AN XY: 73080

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.591

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.712

Alfa AF: 0.561 Hom.: 1437

Bravo AF: 0.730

Asia WGS AF: 0.636 AC: 2124 AN: 3342

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	4.4
Dann	Benign	0.45
RBP_binding_hub_radar		0.91
RBP_regulation_power_radar		2.2

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: rs10278185; hg19: chr7-157130029; COSMIC: COSV51100451; COSMIC: COSV51100451;