Variant 6-44253152-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_007355.4(HSP90AB1):c.1839C>T(p.Asp613=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00609 in 1,614,216 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0063 ( 57 hom. )

Consequence

HSP90AB1
NM_007355.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.30

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 6-44253152-C-T is Benign according to our data. Variant chr6-44253152-C-T is described in ClinVar as [Benign]. Clinvar id is 721181.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.3 with no splicing effect.

BS2

High AC in GnomAd4 at 669 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSP90AB1	NM_007355.4 linkuse as main transcript	c.1839C>T	p.Asp613=	synonymous_variant	11/12	ENST00000371646.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
HSP90AB1	ENST00000371646.10 linkuse as main transcript	c.1839C>T	p.Asp613=	synonymous_variant	11/12	1	NM_007355.4	P1
HSP90AB1	ENST00000353801.7 linkuse as main transcript	c.1839C>T	p.Asp613=	synonymous_variant	11/12	1		P1
HSP90AB1	ENST00000371554.2 linkuse as main transcript	c.1839C>T	p.Asp613=	synonymous_variant	11/12	5		P1
HSP90AB1	ENST00000620073.4 linkuse as main transcript	c.1839C>T	p.Asp613=	synonymous_variant	11/12	5		P1

Frequencies

GnomAD3 genomes

AF:

0.00441

AC:

671

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00616

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00475

AC:

1194

AN:

251470

Hom.:

AF XY:

0.00539

AC XY:

732

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00129

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00327

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0127

Gnomad FIN exome

AF:

0.00129

Gnomad NFE exome

AF:

0.00554

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00627

AC:

9168

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00643

AC XY:

4679

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00210

Gnomad4 ASJ exome

AF:

0.00318

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0124

Gnomad4 FIN exome

AF:

0.00103

Gnomad4 NFE exome

AF:

0.00672

Gnomad4 OTH exome

AF:

0.00551

GnomAD4 genome

AF:

0.00439

AC:

669

AN:

152354

Hom.:

Cov.:

AF XY:

0.00427

AC XY:

318

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00529

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0145

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00616

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00547

Hom.:

Bravo

AF:

0.00410

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.00589

EpiControl

AF:

0.00593

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

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.93

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