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GeneBe

12-103932343-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003299.3(HSP90B1):c.219G>A(p.Ser73=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0067 in 1,612,802 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 5 hom., cov: 33)
Exomes 𝑓: 0.0069 ( 42 hom. )

Consequence

HSP90B1
NM_003299.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.131
Variant links:
Genes affected
HSP90B1 (HGNC:12028): (heat shock protein 90 beta family member 1) This gene encodes a member of a family of adenosine triphosphate(ATP)-metabolizing molecular chaperones with roles in stabilizing and folding other proteins. The encoded protein is localized to melanosomes and the endoplasmic reticulum. Expression of this protein is associated with a variety of pathogenic states, including tumor formation. There is a microRNA gene located within the 5' exon of this gene. There are pseudogenes for this gene on chromosomes 1 and 15. [provided by RefSeq, Aug 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 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=-0.6).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-103932343-G-A is Benign according to our data. Variant chr12-103932343-G-A is described in ClinVar as [Benign]. Clinvar id is 713994.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=0.131 with no splicing effect.
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 683 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HSP90B1NM_003299.3 linkuse as main transcriptc.219G>A p.Ser73= synonymous_variant 3/18 ENST00000299767.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HSP90B1ENST00000299767.10 linkuse as main transcriptc.219G>A p.Ser73= synonymous_variant 3/181 NM_003299.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00449
AC:
683
AN:
152084
Hom.:
5
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00159
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00223
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00123
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00828
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00388
AC:
973
AN:
250920
Hom.:
4
AF XY:
0.00380
AC XY:
515
AN XY:
135652
show subpopulations
Gnomad AFR exome
AF:
0.00166
Gnomad AMR exome
AF:
0.000493
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000295
Gnomad FIN exome
AF:
0.000924
Gnomad NFE exome
AF:
0.00780
Gnomad OTH exome
AF:
0.00245
GnomAD4 exome
AF:
0.00693
AC:
10124
AN:
1460600
Hom.:
42
Cov.:
29
AF XY:
0.00661
AC XY:
4801
AN XY:
726684
show subpopulations
Gnomad4 AFR exome
AF:
0.00111
Gnomad4 AMR exome
AF:
0.000515
Gnomad4 ASJ exome
AF:
0.000153
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000383
Gnomad4 FIN exome
AF:
0.00120
Gnomad4 NFE exome
AF:
0.00873
Gnomad4 OTH exome
AF:
0.00428
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00449
AC:
683
AN:
152202
Hom.:
5
Cov.:
33
AF XY:
0.00356
AC XY:
265
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.00159
Gnomad4 AMR
AF:
0.00222
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00123
Gnomad4 NFE
AF:
0.00828
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00587
Hom.:
2
Bravo
AF:
0.00399
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00622
EpiControl
AF:
0.00670

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 testingInvitaeApr 25, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
Cadd
Benign
11
Dann
Benign
0.69
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: rs11547724; hg19: chr12-104326121; API