Variant 6-44248746-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.117C>T(p.Phe39=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00877 in 1,613,900 control chromosomes in the GnomAD database, including 120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 18 hom., cov: 33)

Exomes 𝑓: 0.0089 ( 102 hom. )

Consequence

HSP90AB1
NM_007355.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.318

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=-0.41).

BP6

Variant 6-44248746-C-T is Benign according to our data. Variant chr6-44248746-C-T is described in ClinVar as [Benign]. Clinvar id is 778005.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.318 with no splicing effect.

BS2

High AC in GnomAd4 at 1170 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSP90AB1	NM_007355.4 linkuse as main transcript	c.117C>T	p.Phe39=	synonymous_variant	2/12	ENST00000371646.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
HSP90AB1	ENST00000371646.10 linkuse as main transcript	c.117C>T	p.Phe39=	synonymous_variant	2/12	1	NM_007355.4	P1
HSP90AB1	ENST00000353801.7 linkuse as main transcript	c.117C>T	p.Phe39=	synonymous_variant	2/12	1		P1
HSP90AB1	ENST00000371554.2 linkuse as main transcript	c.117C>T	p.Phe39=	synonymous_variant	2/12	5		P1
HSP90AB1	ENST00000620073.4 linkuse as main transcript	c.117C>T	p.Phe39=	synonymous_variant	2/12	5		P1

Frequencies

GnomAD3 genomes

AF:

0.00769

AC:

1170

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00166

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.0465

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00830

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00882

AC:

2215

AN:

251274

Hom.:

AF XY:

0.00831

AC XY:

1129

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00101

Gnomad FIN exome

AF:

0.0465

Gnomad NFE exome

AF:

0.00873

Gnomad OTH exome

AF:

0.00913

GnomAD4 exome

AF:

0.00889

AC:

12989

AN:

1461604

Hom.:

102

Cov.:

AF XY:

0.00875

AC XY:

6361

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.00316

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000812

Gnomad4 FIN exome

AF:

0.0459

Gnomad4 NFE exome

AF:

0.00887

Gnomad4 OTH exome

AF:

0.00687

GnomAD4 genome

AF:

0.00768

AC:

1170

AN:

152296

Hom.:

Cov.:

AF XY:

0.00900

AC XY:

670

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.0465

Gnomad4 NFE

AF:

0.00830

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00707

Hom.:

Bravo

AF:

0.00467

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00780

EpiControl

AF:

0.00640

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

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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