chr12-103930488-G-A

Variant names:

• chr12-103930488-G-A
• rs17797090
• NM_003299.3:c.-28G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.905
• Publications: 18 publications found

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]

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]

ENSG00000293399 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003299.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSP90B1	NM_003299.3	MANE Select	c.-28G>A		5_prime_UTR	Exon 1 of 18	NP_003290.1
	MIR3652	NR_037425.1		n.64G>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSP90B1	ENST00000299767.10	TSL:1 MANE Select	c.-28G>A		5_prime_UTR	Exon 1 of 18	ENSP00000299767.4
	HSP90B1	ENST00000614327.2	TSL:1	c.-28G>A		5_prime_UTR	Exon 1 of 17	ENSP00000477660.2
	HSP90B1	ENST00000540297.7	TSL:3	n.126G>A		non_coding_transcript_exon	Exon 1 of 5

Frequencies

GnomAD3 genomes AF: 0.0796 AC: 12103 AN: 152124 Hom.: 534 Cov.: 32

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

GnomAD2 exomes AF: 0.0685 AC: 15302 AN: 223390 AF XY: 0.0711

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 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.: 31 AF XY: 0.0854 AC XY: 60910 AN XY: 713334

African (AFR) AF: 0.0733 AC: 2351 AN: 32090

American (AMR) AF: 0.0524 AC: 2172 AN: 41420

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 3217 AN: 25174

East Asian (EAS) AF: 0.00174 AC: 65 AN: 37362

South Asian (SAS) AF: 0.0841 AC: 7047 AN: 83822

European-Finnish (FIN) AF: 0.0638 AC: 3356 AN: 52624

Middle Eastern (MID) AF: 0.135 AC: 761 AN: 5618

European-Non Finnish (NFE) AF: 0.0893 AC: 98109 AN: 1098566

Other (OTH) AF: 0.0903 AC: 5357 AN: 59316

GnomAD4 genome AF: 0.0795 AC: 12099 AN: 152242 Hom.: 533 Cov.: 32 AF XY: 0.0792 AC XY: 5898 AN XY: 74444

African (AFR) AF: 0.0716 AC: 2973 AN: 41532

American (AMR) AF: 0.0831 AC: 1272 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3470

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5182

South Asian (SAS) AF: 0.0749 AC: 362 AN: 4830

European-Finnish (FIN) AF: 0.0662 AC: 703 AN: 10616

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0891 AC: 6061 AN: 68002

Other (OTH) AF: 0.0892 AC: 188 AN: 2108

Alfa AF: 0.0881 Hom.: 1105

Bravo AF: 0.0792

Asia WGS AF: 0.0570 AC: 198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		0.91
PromoterAI		0.12	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2
Mutation Taster		=298/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17797090; hg19: chr12-104324266;