Genetic Variant NM_006145.3: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJB1	NM_006145.3 link	c.*555C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000254322.3	NP_006136.1	P25685-1Q6FHS4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJB1	ENST00000254322.3 link	c.*555C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_006145.3	ENSP00000254322.1		P25685-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over