chr19-14516238-G-A

Variant names:

• chr19-14516238-G-A
• rs4926222
• NM_006145.3:c.793-68C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006145.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB1	NM_006145.3	MANE Select	c.793-68C>T		intron	N/A	NP_006136.1
	DNAJB1	NM_001300914.2		c.493-68C>T		intron	N/A	NP_001287843.1
	DNAJB1	NM_001313964.2		c.493-68C>T		intron	N/A	NP_001300893.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB1	ENST00000254322.3	TSL:1 MANE Select	c.793-68C>T		intron	N/A	ENSP00000254322.1
	DNAJB1	ENST00000595139.2	TSL:4	c.*198C>T		3_prime_UTR	Exon 2 of 2	ENSP00000469221.2
	DNAJB1	ENST00000676577.1		c.592-68C>T		intron	N/A	ENSP00000503351.1

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

African (AFR) AF: 0.913 AC: 28713 AN: 31444

American (AMR) AF: 0.701 AC: 26761 AN: 38166

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 22776 AN: 25266

East Asian (EAS) AF: 0.336 AC: 13188 AN: 39244

South Asian (SAS) AF: 0.820 AC: 68291 AN: 83328

European-Finnish (FIN) AF: 0.853 AC: 40523 AN: 47516

Middle Eastern (MID) AF: 0.872 AC: 4895 AN: 5614

European-Non Finnish (NFE) AF: 0.849 AC: 910578 AN: 1072430

Other (OTH) AF: 0.815 AC: 47626 AN: 58414

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

African (AFR) AF: 0.907 AC: 37664 AN: 41508

American (AMR) AF: 0.750 AC: 11432 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 3110 AN: 3468

East Asian (EAS) AF: 0.338 AC: 1745 AN: 5156

South Asian (SAS) AF: 0.813 AC: 3907 AN: 4808

European-Finnish (FIN) AF: 0.845 AC: 8926 AN: 10560

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.855 AC: 58099 AN: 67966

Other (OTH) AF: 0.823 AC: 1739 AN: 2114

Alfa AF: 0.845 Hom.: 231455

Bravo AF: 0.832

Asia WGS AF: 0.604 AC: 2102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.28
DANN	Benign	0.50
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=13/87	disease causing

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

Other links and lift over

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