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GeneBe

19-14516099-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_006145.3(DNAJB1):c.864T>C(p.Val288=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,613,854 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0087 ( 26 hom., cov: 32)
Exomes 𝑓: 0.0027 ( 70 hom. )

Consequence

DNAJB1
NM_006145.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.22
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-14516099-A-G is Benign according to our data. Variant chr19-14516099-A-G is described in ClinVar as [Benign]. Clinvar id is 788141.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.22 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0087 (1325/152234) while in subpopulation SAS AF= 0.0288 (139/4826). AF 95% confidence interval is 0.0251. There are 26 homozygotes in gnomad4. There are 684 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1318 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DNAJB1NM_006145.3 linkuse as main transcriptc.864T>C p.Val288= synonymous_variant 3/3 ENST00000254322.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DNAJB1ENST00000254322.3 linkuse as main transcriptc.864T>C p.Val288= synonymous_variant 3/31 NM_006145.3 P1P25685-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00866
AC:
1318
AN:
152116
Hom.:
25
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0264
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00282
Gnomad ASJ
AF:
0.00720
Gnomad EAS
AF:
0.000576
Gnomad SAS
AF:
0.0282
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.00590
AC:
1481
AN:
251138
Hom.:
15
AF XY:
0.00673
AC XY:
914
AN XY:
135782
show subpopulations
Gnomad AFR exome
AF:
0.0269
Gnomad AMR exome
AF:
0.00140
Gnomad ASJ exome
AF:
0.00744
Gnomad EAS exome
AF:
0.000436
Gnomad SAS exome
AF:
0.0287
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000211
Gnomad OTH exome
AF:
0.00196
GnomAD4 exome
AF:
0.00269
AC:
3931
AN:
1461620
Hom.:
70
Cov.:
32
AF XY:
0.00343
AC XY:
2491
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.0255
Gnomad4 AMR exome
AF:
0.00164
Gnomad4 ASJ exome
AF:
0.00746
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.0284
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000791
Gnomad4 OTH exome
AF:
0.00414
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00870
AC:
1325
AN:
152234
Hom.:
26
Cov.:
32
AF XY:
0.00919
AC XY:
684
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.0264
Gnomad4 AMR
AF:
0.00281
Gnomad4 ASJ
AF:
0.00720
Gnomad4 EAS
AF:
0.000578
Gnomad4 SAS
AF:
0.0288
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00427
Alfa
AF:
0.00379
Hom.:
1
Bravo
AF:
0.00897
Asia WGS
AF:
0.0160
AC:
57
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 06, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
Cadd
Benign
11
Dann
Benign
0.79
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2230251; hg19: chr19-14626911; API