Genetic Variant DNAJB1:c.*555C>T (chr19-14515385-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.64

Publications

20 publications found

Variant links:

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]

DNAJB1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAJB1	NM_006145.3	MANE Select	c.*555C>T	3_prime_UTR	Exon 3 of 3	NP_006136.1	Q6FHS4
DNAJB1	NM_001300914.2		c.*555C>T	3_prime_UTR	Exon 3 of 3	NP_001287843.1	P25685-2
DNAJB1	NM_001313964.2		c.*555C>T	3_prime_UTR	Exon 4 of 4	NP_001300893.1	P25685-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAJB1	ENST00000254322.3	TSL:1 MANE Select	c.*555C>T	3_prime_UTR	Exon 3 of 3	ENSP00000254322.1	P25685-1
DNAJB1	ENST00000595139.2	TSL:4	c.*1051C>T	3_prime_UTR	Exon 2 of 2	ENSP00000469221.2	M0QXK0
DNAJB1	ENST00000676577.1		c.*555C>T	3_prime_UTR	Exon 3 of 3	ENSP00000503351.1	A0A7I2V3K7

Frequencies

GnomAD3 genomes

AF:

0.0610

AC:

9284

AN:

152146

Hom.:

331

Cov.:

show subpopulations

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:

AN:

990

Hom.:

Cov.:

AF XY:

0.0592

AC XY:

AN XY:

608

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0352

AC:

AN:

142

European-Finnish (FIN)

AF:

0.0498

AC:

AN:

462

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0640

AC:

AN:

328

Other (OTH)

AF:

0.0714

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0610

AC:

9286

AN:

152264

Hom.:

331

Cov.:

AF XY:

0.0596

AC XY:

4439

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0794

AC:

3298

AN:

41550

American (AMR)

AF:

0.0496

AC:

759

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0469

AC:

163

AN:

3472

East Asian (EAS)

AF:

0.00231

AC:

AN:

5188

South Asian (SAS)

AF:

0.0211

AC:

102

AN:

4830

European-Finnish (FIN)

AF:

0.0632

AC:

670

AN:

10602

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0583

AC:

3968

AN:

68016

Other (OTH)

AF:

0.0744

AC:

157

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

445

890

1336

1781

2226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0563

Hom.:

100

Bravo

AF:

0.0623

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over