14-102088454-G-C

Position:

• chr14-102088454-G-C

Variant summary

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

The NM_001017963.3(HSP90AA1):​c.367-2076C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 152,198 control chromosomes in the GnomAD database, including 42,704 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 0.71 (42704 hom., cov: 33)
• Consequence: HSP90AA1 NM_001017963.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.650

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSP90AA1	NM_001017963.3	c.367-2076C>G		intron_variant			NP_001017963.2
HSP90AA1	XM_011536718.3	c.364-2076C>G		intron_variant			XP_011535020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSP90AA1	ENST00000334701.11	c.367-2076C>G		intron_variant		1		ENSP00000335153.7
HSP90AA1	ENST00000557234.1	n.156-2076C>G		intron_variant		3		ENSP00000452241.1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108482 AN: 152080 Hom.: 42702 Cov.: 33

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.713 AC: 108498 AN: 152198 Hom.: 42704 Cov.: 33 AF XY: 0.716 AC XY: 53301 AN XY: 74422

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.807

Gnomad4 ASJ AF: 0.822

Gnomad4 EAS AF: 0.789

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.869

Gnomad4 NFE AF: 0.874

Gnomad4 OTH AF: 0.730

Alfa AF: 0.780 Hom.: 5832

Bravo AF: 0.692

Asia WGS AF: 0.782 AC: 2718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.5
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3809386; hg19: chr14-102554791;