rs17034977

Positions:

• chr12-103945514-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003299.3(HSP90B1):​c.2028-1104A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0845 in 152,192 control chromosomes in the GnomAD database, including 721 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 0.085 (721 hom., cov: 32)
• Consequence: HSP90B1 NM_003299.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327

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]

UQCC6 (HGNC:34450): (ubiquinol-cytochrome c reductase complex assembly factor 6) Involved in mitochondrial respiratory chain complex III assembly. Located in mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSP90B1	NM_003299.3	c.2028-1104A>C		intron_variant		ENST00000299767.10	NP_003290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSP90B1	ENST00000299767.10	c.2028-1104A>C		intron_variant		1	NM_003299.3	ENSP00000299767	P1

Frequencies

GnomAD3 genomes AF: 0.0845 AC: 12851 AN: 152074 Hom.: 719 Cov.: 32

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0565

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0914

Gnomad OTH AF: 0.0805

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0845 AC: 12864 AN: 152192 Hom.: 721 Cov.: 32 AF XY: 0.0884 AC XY: 6574 AN XY: 74392

Gnomad4 AFR AF: 0.0409

Gnomad4 AMR AF: 0.0564

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.0914

Gnomad4 OTH AF: 0.0797

Alfa AF: 0.0878 Hom.: 125

Bravo AF: 0.0766

Asia WGS AF: 0.173 AC: 602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs17034977; hg19: chr12-104339292;