Genetic Variant HSPA1B:c.-178C>G (chr6-31827773-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005346.6(HSPA1B):c.-178C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000763 in 1,389,236 control chromosomes in the GnomAD database, including 1 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 0.00043 ( 1 hom., cov: 31)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

HSPA1B
NM_005346.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.05

Publications

40 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 -2 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.018).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005346.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA1B	NM_005346.6	MANE Select	c.-178C>G		5_prime_UTR	Exon 1 of 1	NP_005337.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HSPA1B	ENST00000375650.5	TSL:6 MANE Select	c.-178C>G	5_prime_UTR	Exon 1 of 1	ENSP00000364801.3
SNHG32	ENST00000718216.1		n.364+415C>G	intron	N/A
SNHG32	ENST00000718219.1		n.184+5472C>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000421

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000847

AC:

AN:

141746

AF XY:

0.0000906

show subpopulations

Gnomad AFR exome

AF:

0.00177

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000331

AC:

AN:

1237052

Hom.:

Cov.:

AF XY:

0.0000259

AC XY:

AN XY:

617636

show subpopulations

African (AFR)

AF:

0.00126

AC:

AN:

28542

American (AMR)

AF:

0.00

AC:

AN:

35438

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24008

East Asian (EAS)

AF:

0.00

AC:

AN:

35054

South Asian (SAS)

AF:

0.00

AC:

AN:

76346

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5408

European-Non Finnish (NFE)

AF:

0.00000107

AC:

AN:

938876

Other (OTH)

AF:

0.0000758

AC:

AN:

52790

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.000427

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.00152

AC:

AN:

41498

American (AMR)

AF:

0.0000655

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67994

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00

Hom.:

2487

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.21

(source)

DANN

Benign

0.46

PhyloP100

-2.0

PromoterAI

0.014

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over