dbSNP rs35074133: HSP90AB1:c.-64T>A (chr6-44247132-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_007355.4(HSP90AB1):c.-64T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0318 in 152,188 control chromosomes in the GnomAD database, including 119 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 0.032 ( 119 hom., cov: 32)

Exomes 𝑓: 0.044 ( 0 hom. )

Consequence

HSP90AB1
NM_007355.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.90

Publications

6 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0318 (4839/152120) while in subpopulation NFE AF = 0.049 (3333/67970). AF 95% confidence interval is 0.0476. There are 119 homozygotes in GnomAd4. There are 2257 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 4839 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSP90AB1	NM_007355.4 link	c.-64T>A		5_prime_UTR_variant	Exon 1 of 12	ENST00000371646.10	NP_031381.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
HSP90AB1	ENST00000371646.10 link	c.-64T>A	5_prime_UTR_variant	Exon 1 of 12	1	NM_007355.4	ENSP00000360709.5
HSP90AB1	ENST00000353801.7 link	c.-77T>A	5_prime_UTR_variant	Exon 1 of 12	1		ENSP00000325875.3
HSP90AB1	ENST00000620073.4 link	c.-1+788T>A	intron_variant	Intron 1 of 11	5		ENSP00000481908.1

Frequencies

GnomAD3 genomes

AF:

0.0318

AC:

4839

AN:

152002

Hom.:

119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00883

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0151

Gnomad ASJ

AF:

0.0332

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0149

Gnomad FIN

AF:

0.0573

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0490

Gnomad OTH

AF:

0.0268

GnomAD4 exome

AF:

0.0441

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0208

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.100

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0400

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0318

AC:

4839

AN:

152120

Hom.:

119

Cov.:

AF XY:

0.0304

AC XY:

2257

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.00881

AC:

366

AN:

41552

American (AMR)

AF:

0.0151

AC:

231

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0332

AC:

115

AN:

3462

East Asian (EAS)

AF:

0.000579

AC:

AN:

5180

South Asian (SAS)

AF:

0.0154

AC:

AN:

4748

European-Finnish (FIN)

AF:

0.0573

AC:

608

AN:

10606

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0490

AC:

3333

AN:

67970

Other (OTH)

AF:

0.0265

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

241

483

724

966

1207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0155

Hom.:

Bravo

AF:

0.0282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.024

(source)

DANN

Benign

0.51

PhyloP100

-3.9

PromoterAI

-0.031

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over