dbSNP rs2236659: HSPA8:c.-132T>C (chr11-123062473-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000876974.1(HSPA8):c.-132T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,232 control chromosomes in the GnomAD database, including 1,475 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 0.11 ( 1475 hom., cov: 33)

Exomes 𝑓: 0.039 ( 0 hom. )

Consequence

HSPA8
ENST00000876974.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.175

Publications

9 publications found

Variant links:

Genes affected

HSPA8 (HGNC:5241): (heat shock protein family A (Hsp70) member 8) This gene encodes a member of the heat shock protein 70 family, which contains both heat-inducible and constitutively expressed members. This protein belongs to the latter group, which are also referred to as heat-shock cognate proteins. It functions as a chaperone, and binds to nascent polypeptides to facilitate correct folding. It also functions as an ATPase in the disassembly of clathrin-coated vesicles during transport of membrane components through the cell. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

HSPA8 links:

ENSG00000288061 (HGNC:):

ENSG00000288061 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000876974.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.76).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000876974.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HSPA8	ENST00000876974.1		c.-132T>C	5_prime_UTR	Exon 1 of 9	ENSP00000547033.1
HSPA8	ENST00000935611.1		c.-6+86T>C	intron	N/A	ENSP00000605670.1
HSPA8	ENST00000525624.5	TSL:5	c.-6+277T>C	intron	N/A	ENSP00000435154.1	E9PLF4

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16375

AN:

152038

Hom.:

1462

Cov.:

show subpopulations

Gnomad AFR

AF:

0.234

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0786

Gnomad ASJ

AF:

0.0303

Gnomad EAS

AF:

0.195

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.0322

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0427

Gnomad OTH

AF:

0.0821

GnomAD4 exome

AF:

0.0395

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0313

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0385

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.108

AC:

16427

AN:

152156

Hom.:

1475

Cov.:

AF XY:

0.109

AC XY:

8120

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.235

AC:

9749

AN:

41512

American (AMR)

AF:

0.0787

AC:

1203

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0303

AC:

105

AN:

3470

East Asian (EAS)

AF:

0.195

AC:

1002

AN:

5142

South Asian (SAS)

AF:

0.194

AC:

936

AN:

4832

European-Finnish (FIN)

AF:

0.0322

AC:

342

AN:

10618

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0427

AC:

2903

AN:

67980

Other (OTH)

AF:

0.0812

AC:

171

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

728

1455

2183

2910

3638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<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:

0.0856

Hom.:

134

Bravo

AF:

0.115

Asia WGS

AF:

0.165

AC:

574

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

-0.17

PromoterAI

0.021

Neutral

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over