dbSNP rs35682610: HSPA1B:p.Val570Val (chr6-31829660-T-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_005346.6(HSPA1B):c.1710T>G(p.Val570Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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 0.016 ( 17 hom., cov: 23)

Exomes 𝑓: 0.0030 ( 196 hom. )

Failed GnomAD Quality Control

Consequence

HSPA1B
NM_005346.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0420

Publications

4 publications found

Variant links:

Genes affected

HSPA1B (HGNC:5233): (heat shock protein family A (Hsp70) member 1B) This intronless gene encodes a 70kDa heat shock protein which is a member of the heat shock protein 70 family. In conjuction with other heat shock proteins, this protein stabilizes existing proteins against aggregation and mediates the folding of newly translated proteins in the cytosol and in organelles. It is also involved in the ubiquitin-proteasome pathway through interaction with the AU-rich element RNA-binding protein 1. The gene is located in the major histocompatibility complex class III region, in a cluster with two closely related genes which encode similar proteins. [provided by RefSeq, Jul 2008]

HSPA1B links:

SNHG32 (HGNC:19078): (small nucleolar RNA host gene 32) Predicted to enable double-stranded RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

SNHG32 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

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

BP7

Synonymous conserved (PhyloP=0.042 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA1B	NM_005346.6 link	c.1710T>G	p.Val570Val	synonymous_variant	Exon 1 of 1	ENST00000375650.5	NP_005337.2	P0DMV8-1P0DMV9A8K5I0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA1B	ENST00000375650.5 link	c.1710T>G	p.Val570Val	synonymous_variant	Exon 1 of 1	6	NM_005346.6	ENSP00000364801.3		P0DMV9

Frequencies

GnomAD3 genomes

AF:

0.0161

AC:

2434

AN:

151066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0263

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.0230

Gnomad EAS

AF:

0.0244

Gnomad SAS

AF:

0.0157

Gnomad FIN

AF:

0.00490

Gnomad MID

AF:

0.0192

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.0168

GnomAD2 exomes

AF:

0.000901

AC:

218

AN:

242016

AF XY:

0.000894

show subpopulations

Gnomad AFR exome

AF:

0.00220

Gnomad AMR exome

AF:

0.000472

Gnomad ASJ exome

AF:

0.00123

Gnomad EAS exome

AF:

0.00166

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000725

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00305

AC:

4398

AN:

1444024

Hom.:

196

Cov.:

AF XY:

0.00310

AC XY:

2228

AN XY:

718082

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00748

AC:

245

AN:

32738

American (AMR)

AF:

0.00374

AC:

165

AN:

44088

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

287

AN:

25624

East Asian (EAS)

AF:

0.0211

AC:

816

AN:

38700

South Asian (SAS)

AF:

0.00189

AC:

159

AN:

83914

European-Finnish (FIN)

AF:

0.00253

AC:

132

AN:

52098

Middle Eastern (MID)

AF:

0.00335

AC:

AN:

5670

European-Non Finnish (NFE)

AF:

0.00207

AC:

2279

AN:

1101452

Other (OTH)

AF:

0.00495

AC:

296

AN:

59740

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

369

738

1106

1475

1844

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0161

AC:

2436

AN:

151184

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1156

AN XY:

73934

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0262

AC:

1078

AN:

41072

American (AMR)

AF:

0.0138

AC:

209

AN:

15182

Ashkenazi Jewish (ASJ)

AF:

0.0230

AC:

AN:

3442

East Asian (EAS)

AF:

0.0244

AC:

125

AN:

5120

South Asian (SAS)

AF:

0.0157

AC:

AN:

4784

European-Finnish (FIN)

AF:

0.00490

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0241

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0114

AC:

772

AN:

67672

Other (OTH)

AF:

0.0167

AC:

AN:

2102

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.333

Heterozygous variant carriers

129

258

387

516

645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0128

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

9.0

(source)

DANN

Benign

0.75

PhyloP100

0.042

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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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