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GeneBe

19-14516147-G-A

Variant summary

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

The NM_006145.3(DNAJB1):c.816C>T(p.Asn272=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,613,218 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0078 ( 22 hom., cov: 32)
Exomes 𝑓: 0.00094 ( 14 hom. )

Consequence

DNAJB1
NM_006145.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.11
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=-0.59).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-14516147-G-A is Benign according to our data. Variant chr19-14516147-G-A is described in ClinVar as [Benign]. Clinvar id is 715182.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=-3.11 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0078 (1187/152206) while in subpopulation AFR AF= 0.0264 (1096/41530). AF 95% confidence interval is 0.0251. There are 22 homozygotes in gnomad4. There are 575 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 1183 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DNAJB1NM_006145.3 linkuse as main transcriptc.816C>T p.Asn272= synonymous_variant 3/3 ENST00000254322.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DNAJB1ENST00000254322.3 linkuse as main transcriptc.816C>T p.Asn272= synonymous_variant 3/31 NM_006145.3 P1P25685-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00778
AC:
1183
AN:
152088
Hom.:
21
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0264
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00282
Gnomad ASJ
AF:
0.00721
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00233
AC:
584
AN:
250202
Hom.:
3
AF XY:
0.00176
AC XY:
238
AN XY:
135404
show subpopulations
Gnomad AFR exome
AF:
0.0271
Gnomad AMR exome
AF:
0.00138
Gnomad ASJ exome
AF:
0.00727
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000463
Gnomad NFE exome
AF:
0.000150
Gnomad OTH exome
AF:
0.00131
GnomAD4 exome
AF:
0.000940
AC:
1373
AN:
1461012
Hom.:
14
Cov.:
32
AF XY:
0.000865
AC XY:
629
AN XY:
726896
show subpopulations
Gnomad4 AFR exome
AF:
0.0255
Gnomad4 AMR exome
AF:
0.00169
Gnomad4 ASJ exome
AF:
0.00735
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000944
Gnomad4 OTH exome
AF:
0.00229
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00780
AC:
1187
AN:
152206
Hom.:
22
Cov.:
32
AF XY:
0.00773
AC XY:
575
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.0264
Gnomad4 AMR
AF:
0.00281
Gnomad4 ASJ
AF:
0.00721
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00239
Hom.:
3
Bravo
AF:
0.00882
Asia WGS
AF:
0.00115
AC:
4
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.000237

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
-0.59
Cadd
Benign
1.2
Dann
Benign
0.94
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: rs2230250; hg19: chr19-14626959; API