chr14-102088454-G-C

Variant names:

• chr14-102088454-G-C
• rs3809386
• ENST00000334701.11:c.367-2076C>G

Variant summary

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

The ENST00000334701.11(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 ENST00000334701.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.650
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000334701.11. 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
	HSP90AA1	NM_001017963.3		c.367-2076C>G		intron	N/A	NP_001017963.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSP90AA1	ENST00000334701.11	TSL:1	c.367-2076C>G		intron	N/A	ENSP00000335153.7
	HSP90AA1	ENST00000557234.1	TSL:3	n.156-2076C>G		intron	N/A	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

African (AFR) AF: 0.345 AC: 14322 AN: 41504

American (AMR) AF: 0.807 AC: 12340 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2852 AN: 3470

East Asian (EAS) AF: 0.789 AC: 4080 AN: 5172

South Asian (SAS) AF: 0.758 AC: 3656 AN: 4824

European-Finnish (FIN) AF: 0.869 AC: 9213 AN: 10598

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.874 AC: 59423 AN: 68020

Other (OTH) AF: 0.730 AC: 1541 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.5
DANN	Benign	0.42
PhyloP100		0.65
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3809386; hg19: chr14-102554791;