rs4926222

Positions:

• chr19-14516238-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006145.3(DNAJB1):​c.793-68C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 1,553,450 control chromosomes in the GnomAD database, including 543,450 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.84 (54616 hom., cov: 30)
  • Exomes 𝑓: 0.83 (488834 hom.)
• Consequence: DNAJB1 NM_006145.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

Genes affected

DNAJB1 (HGNC:5270): (DnaJ heat shock protein family (Hsp40) member B1) This gene encodes a member of the DnaJ or Hsp40 (heat shock protein 40 kD) family of proteins. 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. The encoded protein is a molecular chaperone that stimulates the ATPase activity of Hsp70 heat-shock proteins in order to promote protein folding and prevent misfolded protein aggregation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJB1	NM_006145.3	c.793-68C>T		intron_variant		ENST00000254322.3	NP_006136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJB1	ENST00000254322.3	c.793-68C>T		intron_variant		1	NM_006145.3	ENSP00000254322.1

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127660 AN: 151910 Hom.: 54558 Cov.: 30

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.751

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.832

GnomAD4 exome AF: 0.830 AC: 1163351 AN: 1401422 Hom.: 488834 Cov.: 24 AF XY: 0.831 AC XY: 581393 AN XY: 699800

Gnomad4 AFR exome AF: 0.913

Gnomad4 AMR exome AF: 0.701

Gnomad4 ASJ exome AF: 0.901

Gnomad4 EAS exome AF: 0.336

Gnomad4 SAS exome AF: 0.820

Gnomad4 FIN exome AF: 0.853

Gnomad4 NFE exome AF: 0.849

Gnomad4 OTH exome AF: 0.815

GnomAD4 genome AF: 0.840 AC: 127764 AN: 152028 Hom.: 54616 Cov.: 30 AF XY: 0.835 AC XY: 62034 AN XY: 74304

Gnomad4 AFR AF: 0.907

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.813

Gnomad4 FIN AF: 0.845

Gnomad4 NFE AF: 0.855

Gnomad4 OTH AF: 0.823

Alfa AF: 0.845 Hom.: 109382

Bravo AF: 0.832

Asia WGS AF: 0.604 AC: 2102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.28
DANN	Benign	0.50
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

Other links and lift over

dbSNP: rs4926222; hg19: chr19-14627050; COSMIC: COSV54317084; COSMIC: COSV54317084;