Genetic Variant HSPA8:c.-5-86G>C (chr11-123061415-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_006597.6(HSPA8):c.-5-86G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,037,656 control chromosomes in the GnomAD database, including 30,804 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 0.28 ( 7122 hom., cov: 32)

Exomes 𝑓: 0.22 ( 23682 hom. )

Consequence

HSPA8
NM_006597.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

Publications

7 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:

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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=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006597.6. 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
	HSPA8	NM_006597.6	MANE Select	c.-5-86G>C		intron	N/A	NP_006588.1	P11142-1
	HSPA8	NM_153201.4		c.-5-86G>C		intron	N/A	NP_694881.1	P11142-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HSPA8	ENST00000534624.6	TSL:1 MANE Select	c.-5-86G>C	intron	N/A	ENSP00000432083.1	P11142-1
HSPA8	ENST00000453788.6	TSL:1	c.-5-86G>C	intron	N/A	ENSP00000404372.2	P11142-2
HSPA8	ENST00000527983.5	TSL:1	n.145-86G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42310

AN:

151954

Hom.:

7101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.459

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.456

Gnomad SAS

AF:

0.325

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.241

GnomAD4 exome

AF:

0.222

AC:

196753

AN:

885584

Hom.:

23682

Cov.:

AF XY:

0.224

AC XY:

101724

AN XY:

454936

show subpopulations

African (AFR)

AF:

0.476

AC:

10414

AN:

21882

American (AMR)

AF:

0.236

AC:

7900

AN:

33440

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

3334

AN:

20712

East Asian (EAS)

AF:

0.440

AC:

14759

AN:

33538

South Asian (SAS)

AF:

0.306

AC:

20545

AN:

67112

European-Finnish (FIN)

AF:

0.179

AC:

7837

AN:

43748

Middle Eastern (MID)

AF:

0.186

AC:

847

AN:

4560

European-Non Finnish (NFE)

AF:

0.196

AC:

121329

AN:

619498

Other (OTH)

AF:

0.238

AC:

9788

AN:

41094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

8159

16318

24476

32635

40794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3550

7100

10650

14200

17750

<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:

0.279

AC:

42389

AN:

152072

Hom.:

7122

Cov.:

AF XY:

0.279

AC XY:

20767

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.460

AC:

19059

AN:

41444

American (AMR)

AF:

0.239

AC:

3653

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

556

AN:

3470

East Asian (EAS)

AF:

0.456

AC:

2354

AN:

5162

South Asian (SAS)

AF:

0.323

AC:

1557

AN:

4814

European-Finnish (FIN)

AF:

0.177

AC:

1876

AN:

10580

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.185

AC:

12577

AN:

68002

Other (OTH)

AF:

0.240

AC:

507

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1461

2923

4384

5846

7307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

424

848

1272

1696

2120

<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:

0.0987

Hom.:

142

Bravo

AF:

0.291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.95

(source)

DANN

Benign

0.13

PhyloP100

-1.2

PromoterAI

-0.024

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over