chr19-14515385-G-A

Position:

• chr19-14515385-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BA1

The NM_006145.3(DNAJB1):​c.*555C>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 0.0609 in 153,254 control chromosomes in the GnomAD database, including 333 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 0.061 (331 hom., cov: 32)
  • Exomes 𝑓: 0.053 (2 hom.)
• Consequence: DNAJB1 NM_006145.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.64

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJB1	NM_006145.3	c.*555C>T		3_prime_UTR_variant	3/3	ENST00000254322.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJB1	ENST00000254322.3	c.*555C>T		3_prime_UTR_variant	3/3	1	NM_006145.3	P1

Frequencies

GnomAD3 genomes AF: 0.0610 AC: 9284 AN: 152146 Hom.: 331 Cov.: 32

Gnomad AFR AF: 0.0796

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.0497

Gnomad ASJ AF: 0.0469

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0211

Gnomad FIN AF: 0.0632

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0583

Gnomad OTH AF: 0.0752

GnomAD4 exome AF: 0.0525 AC: 52 AN: 990 Hom.: 2 Cov.: 0 AF XY: 0.0592 AC XY: 36 AN XY: 608

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0352

Gnomad4 FIN exome AF: 0.0498

Gnomad4 NFE exome AF: 0.0640

Gnomad4 OTH exome AF: 0.0714

GnomAD4 genome AF: 0.0610 AC: 9286 AN: 152264 Hom.: 331 Cov.: 32 AF XY: 0.0596 AC XY: 4439 AN XY: 74452

Gnomad4 AFR AF: 0.0794

Gnomad4 AMR AF: 0.0496

Gnomad4 ASJ AF: 0.0469

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.0211

Gnomad4 FIN AF: 0.0632

Gnomad4 NFE AF: 0.0583

Gnomad4 OTH AF: 0.0744

Alfa AF: 0.0557 Hom.: 93

Bravo AF: 0.0623

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	16
DANN	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1803768; hg19: chr19-14626197;