rs1190596

Positions:

• chr14-102129288-A-G
• chr14-102129288-A-T

Variant summary

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

The ENST00000334701.11(HSP90AA1):​c.155+9962T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 151,884 control chromosomes in the GnomAD database, including 46,894 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 0.78 (46894 hom., cov: 30)
• Consequence: HSP90AA1 ENST00000334701.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

Genes affected

HSP90AA1 (HGNC:5253): (heat shock protein 90 alpha family class A member 1) The protein encoded by this gene is an inducible molecular chaperone that functions as a homodimer. The encoded protein aids in the proper folding of specific target proteins by use of an ATPase activity that is modulated by co-chaperones. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSP90AA1	NM_001017963.3	c.155+9962T>C		intron_variant			NP_001017963.2
HSP90AA1	XM_011536718.3	c.155+9962T>C		intron_variant			XP_011535020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSP90AA1	ENST00000334701.11	c.155+9962T>C		intron_variant		1		ENSP00000335153
HSP90AA1	ENST00000558600.1	c.155+9962T>C		intron_variant		4		ENSP00000489370
HSP90AA1	ENST00000557234.1	c.155+9962T>C		intron_variant, NMD_transcript_variant		3		ENSP00000452241

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118476 AN: 151766 Hom.: 46862 Cov.: 30

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.974

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.781 AC: 118561 AN: 151884 Hom.: 46894 Cov.: 30 AF XY: 0.784 AC XY: 58168 AN XY: 74236

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.856

Gnomad4 ASJ AF: 0.849

Gnomad4 EAS AF: 0.974

Gnomad4 SAS AF: 0.867

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.821

Gnomad4 OTH AF: 0.780

Alfa AF: 0.811 Hom.: 22068

Bravo AF: 0.782

Asia WGS AF: 0.894 AC: 3109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.50
DANN	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1190596; hg19: chr14-102595625;