Variant 12-103930488-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003299.3(HSP90B1):c.-28G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0847 in 1,588,234 control chromosomes in the GnomAD database, including 6,196 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 0.079 ( 533 hom., cov: 32)

Exomes 𝑓: 0.085 ( 5663 hom. )

Consequence

HSP90B1
NM_003299.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.905

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]

HSP90B1 links:

MIR3652 (HGNC:38894): (microRNA 3652) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR3652 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSP90B1	NM_003299.3 linkuse as main transcript	c.-28G>A		5_prime_UTR_variant	1/18	ENST00000299767.10	NP_003290.1
MIR3652	NR_037425.1 linkuse as main transcript	n.64G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSP90B1	ENST00000299767.10 linkuse as main transcript	c.-28G>A		5_prime_UTR_variant	1/18	1	NM_003299.3	ENSP00000299767	P1
MIR3652	ENST00000579335.1 linkuse as main transcript	n.64G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0796

AC:

12103

AN:

152124

Hom.:

534

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0719

Gnomad AMI

AF:

0.0341

Gnomad AMR

AF:

0.0833

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.0745

Gnomad FIN

AF:

0.0662

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.0891

Gnomad OTH

AF:

0.0877

GnomAD3 exomes

AF:

0.0685

AC:

15302

AN:

223390

Hom.:

625

AF XY:

0.0711

AC XY:

8675

AN XY:

122022

show subpopulations

Gnomad AFR exome

AF:

0.0639

Gnomad AMR exome

AF:

0.0482

Gnomad ASJ exome

AF:

0.124

Gnomad EAS exome

AF:

0.00203

Gnomad SAS exome

AF:

0.0814

Gnomad FIN exome

AF:

0.0621

Gnomad NFE exome

AF:

0.0775

Gnomad OTH exome

AF:

0.0856

GnomAD4 exome

AF:

0.0853

AC:

122435

AN:

1435992

Hom.:

5663

Cov.:

AF XY:

0.0854

AC XY:

60910

AN XY:

713334

show subpopulations

Gnomad4 AFR exome

AF:

0.0733

Gnomad4 AMR exome

AF:

0.0524

Gnomad4 ASJ exome

AF:

0.128

Gnomad4 EAS exome

AF:

0.00174

Gnomad4 SAS exome

AF:

0.0841

Gnomad4 FIN exome

AF:

0.0638

Gnomad4 NFE exome

AF:

0.0893

Gnomad4 OTH exome

AF:

0.0903

GnomAD4 genome

AF:

0.0795

AC:

12099

AN:

152242

Hom.:

533

Cov.:

AF XY:

0.0792

AC XY:

5898

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0716

Gnomad4 AMR

AF:

0.0831

Gnomad4 ASJ

AF:

0.128

Gnomad4 EAS

AF:

0.00289

Gnomad4 SAS

AF:

0.0749

Gnomad4 FIN

AF:

0.0662

Gnomad4 NFE

AF:

0.0891

Gnomad4 OTH

AF:

0.0892

Alfa

AF:

0.0895

Hom.:

941

Bravo

AF:

0.0792

Asia WGS

AF:

0.0570

AC:

198

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

DANN

Benign

0.72

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over