rs7003

Positions:

• chr19-14514978-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.*962C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,430 control chromosomes in the GnomAD database, including 2,000 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 0.15 (1998 hom., cov: 32)
  • Exomes 𝑓: 0.095 (2 hom.)
• Consequence: DNAJB1 NM_006145.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJB1	NM_006145.3	c.*962C>T		3_prime_UTR_variant	3/3	ENST00000254322.3	NP_006136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJB1	ENST00000254322.3	c.*962C>T		3_prime_UTR_variant	3/3	1	NM_006145.3	ENSP00000254322	P1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23549 AN: 151932 Hom.: 1999 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0756

Gnomad EAS AF: 0.0114

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.0947 AC: 36 AN: 380 Hom.: 2 Cov.: 0 AF XY: 0.0938 AC XY: 21 AN XY: 224

Gnomad4 FIN exome AF: 0.0946

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.155 AC: 23560 AN: 152050 Hom.: 1998 Cov.: 32 AF XY: 0.151 AC XY: 11242 AN XY: 74328

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0756

Gnomad4 EAS AF: 0.0114

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.158

Alfa AF: 0.147 Hom.: 1156

Bravo AF: 0.160

Asia WGS AF: 0.0870 AC: 304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.3
DANN	Benign	0.75
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1

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: rs7003; hg19: chr19-14625790;