Variant chr14-102082104-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005348.4(HSP90AA1):c.2089+7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,579,444 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 25 hom., cov: 32)

Exomes 𝑓: 0.00091 ( 19 hom. )

Consequence

HSP90AA1
NM_005348.4 splice_region, intron

Scores

Splicing: ADA: 0.00002715

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.305

Variant links:

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]

HSP90AA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 14-102082104-G-T is Benign according to our data. Variant chr14-102082104-G-T is described in ClinVar as [Benign]. Clinvar id is 720694.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00997 (1518/152204) while in subpopulation AFR AF= 0.035 (1451/41500). AF 95% confidence interval is 0.0335. There are 25 homozygotes in gnomad4. There are 748 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1518 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
HSP90AA1	NM_005348.4 linkuse as main transcript	c.2089+7C>A	splice_region_variant, intron_variant	ENST00000216281.13	NP_005339.3	P07900-1K9JA46
HSP90AA1	NM_001017963.3 linkuse as main transcript	c.2455+7C>A	splice_region_variant, intron_variant		NP_001017963.2	P07900-2Q86SX1
HSP90AA1	XM_011536718.3 linkuse as main transcript	c.2452+7C>A	splice_region_variant, intron_variant		XP_011535020.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSP90AA1	ENST00000216281.13 linkuse as main transcript	c.2089+7C>A		splice_region_variant, intron_variant		1	NM_005348.4	ENSP00000216281.8		P07900-1
HSP90AA1	ENST00000334701.11 linkuse as main transcript	c.2455+7C>A		splice_region_variant, intron_variant		1		ENSP00000335153.7		P07900-2

Frequencies

GnomAD3 genomes

AF:

0.00998

AC:

1518

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0351

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00275

AC:

687

AN:

249452

Hom.:

AF XY:

0.00198

AC XY:

268

AN XY:

135068

show subpopulations

Gnomad AFR exome

AF:

0.0361

Gnomad AMR exome

AF:

0.00244

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000980

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000912

AC:

1301

AN:

1427240

Hom.:

Cov.:

AF XY:

0.000766

AC XY:

546

AN XY:

712382

show subpopulations

Gnomad4 AFR exome

AF:

0.0299

Gnomad4 AMR exome

AF:

0.00256

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.0000701

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000731

Gnomad4 OTH exome

AF:

0.00189

GnomAD4 genome

AF:

0.00997

AC:

1518

AN:

152204

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

748

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0350

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00542

Hom.:

Bravo

AF:

0.0112

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.16

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000027

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over