Variant 6-44250488-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_007355.4(HSP90AB1):c.846A>G(p.Leu282=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00271 in 1,613,986 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 14 hom. )

Consequence

HSP90AB1
NM_007355.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.95

Variant links:

Genes affected

HSP90AB1 (HGNC:5258): (heat shock protein 90 alpha family class B member 1) This gene encodes a member of the heat shock protein 90 family; these proteins are involved in signal transduction, protein folding and degradation and morphological evolution. This gene encodes the constitutive form of the cytosolic 90 kDa heat-shock protein and is thought to play a role in gastric apoptosis and inflammation. Alternative splicing results in multiple transcript variants. Pseudogenes have been identified on multiple chromosomes. [provided by RefSeq, Dec 2012]

HSP90AB1 links:

POLR1C (HGNC:):

POLR1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 6-44250488-A-G is Benign according to our data. Variant chr6-44250488-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 711675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 235 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSP90AB1	NM_007355.4 linkuse as main transcript	c.846A>G	p.Leu282=	synonymous_variant	6/12	ENST00000371646.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
HSP90AB1	ENST00000371646.10 linkuse as main transcript	c.846A>G	p.Leu282=	synonymous_variant	6/12	1	NM_007355.4	P1
HSP90AB1	ENST00000353801.7 linkuse as main transcript	c.846A>G	p.Leu282=	synonymous_variant	6/12	1		P1
HSP90AB1	ENST00000371554.2 linkuse as main transcript	c.846A>G	p.Leu282=	synonymous_variant	6/12	5		P1
HSP90AB1	ENST00000620073.4 linkuse as main transcript	c.846A>G	p.Leu282=	synonymous_variant	6/12	5		P1

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

235

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00288

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00132

AC:

333

AN:

251462

Hom.:

AF XY:

0.00121

AC XY:

165

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000924

Gnomad NFE exome

AF:

0.00258

Gnomad OTH exome

AF:

0.000977

GnomAD4 exome

AF:

0.00284

AC:

4144

AN:

1461656

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

1984

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000992

Gnomad4 NFE exome

AF:

0.00357

Gnomad4 OTH exome

AF:

0.00171

GnomAD4 genome

AF:

0.00154

AC:

235

AN:

152330

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

109

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.00288

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00210

Hom.:

Bravo

AF:

0.00151

EpiCase

AF:

0.00294

EpiControl

AF:

0.00261

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	HSP90AB1: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.3

DANN

Benign

0.90

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

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

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