dbSNP rs4935825: HSPA8:c.-5-328T>G (chr11-123061657-A-C) – 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.-5-328T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 384,710 control chromosomes in the GnomAD database, including 21,784 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 ( 7387 hom., cov: 32)

Exomes 𝑓: 0.33 ( 14397 hom. )

Consequence

HSPA8
NM_006597.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.29

Publications

4 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:

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=-0.97).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HSPA8	NM_006597.6 link	c.-5-328T>G	intron_variant	Intron 1 of 8	ENST00000534624.6	NP_006588.1	P11142-1V9HW22Q53HF2
HSPA8	NM_153201.4 link	c.-5-328T>G	intron_variant	Intron 1 of 7		NP_694881.1	P11142-2Q53HF2
HSPA8	XM_011542798.2 link	c.-5-328T>G	intron_variant	Intron 1 of 8		XP_011541100.1	P11142-1V9HW22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA8	ENST00000534624.6 link	c.-5-328T>G		intron_variant	Intron 1 of 8	1	NM_006597.6	ENSP00000432083.1		P11142-1

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42350

AN:

151906

Hom.:

7386

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.507

Gnomad AMR

AF:

0.238

Gnomad ASJ

AF:

0.400

Gnomad EAS

AF:

0.00559

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.360

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.394

Gnomad OTH

AF:

0.314

GnomAD4 exome

AF:

0.332

AC:

77298

AN:

232686

Hom.:

14397

Cov.:

AF XY:

0.329

AC XY:

41246

AN XY:

125398

show subpopulations

African (AFR)

AF:

0.0862

AC:

615

AN:

7138

American (AMR)

AF:

0.224

AC:

2096

AN:

9360

Ashkenazi Jewish (ASJ)

AF:

0.398

AC:

2608

AN:

6556

East Asian (EAS)

AF:

0.00124

AC:

AN:

12132

South Asian (SAS)

AF:

0.272

AC:

9765

AN:

35892

European-Finnish (FIN)

AF:

0.368

AC:

3956

AN:

10750

Middle Eastern (MID)

AF:

0.403

AC:

382

AN:

948

European-Non Finnish (NFE)

AF:

0.391

AC:

53690

AN:

137316

Other (OTH)

AF:

0.331

AC:

4171

AN:

12594

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

2329

4658

6987

9316

11645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

238

476

714

952

1190

<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:

42352

AN:

152024

Hom.:

7387

Cov.:

AF XY:

0.271

AC XY:

20140

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.103

AC:

4280

AN:

41476

American (AMR)

AF:

0.238

AC:

3635

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

1388

AN:

3468

East Asian (EAS)

AF:

0.00560

AC:

AN:

5180

South Asian (SAS)

AF:

0.246

AC:

1187

AN:

4820

European-Finnish (FIN)

AF:

0.360

AC:

3798

AN:

10550

Middle Eastern (MID)

AF:

0.384

AC:

112

AN:

292

European-Non Finnish (NFE)

AF:

0.394

AC:

26798

AN:

67942

Other (OTH)

AF:

0.315

AC:

664

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1447

2895

4342

5790

7237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<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:

0.252

Hom.:

3610

Bravo

AF:

0.263

Asia WGS

AF:

0.141

AC:

493

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.018

(source)

DANN

Benign

0.35

PhyloP100

-4.3

PromoterAI

-0.013

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over