dbSNP rs11823704: HSPA8:c.-5-141G>T (chr11-123061470-C-A) – 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.-5-141G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0174 in 678,938 control chromosomes in the GnomAD database, including 753 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 0.024 ( 179 hom., cov: 32)

Exomes 𝑓: 0.016 ( 574 hom. )

Consequence

HSPA8
NM_006597.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.29

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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HSPA8	NM_006597.6 link	c.-5-141G>T	intron_variant	Intron 1 of 8	ENST00000534624.6	NP_006588.1	P11142-1V9HW22Q53HF2
HSPA8	NM_153201.4 link	c.-5-141G>T	intron_variant	Intron 1 of 7		NP_694881.1	P11142-2Q53HF2
HSPA8	XM_011542798.2 link	c.-5-141G>T	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.-5-141G>T		intron_variant	Intron 1 of 8	1	NM_006597.6	ENSP00000432083.1		P11142-1

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3628

AN:

152148

Hom.:

179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0530

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0118

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.00870

Gnomad FIN

AF:

0.00622

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.0191

GnomAD4 exome

AF:

0.0156

AC:

8208

AN:

526672

Hom.:

574

Cov.:

AF XY:

0.0144

AC XY:

4031

AN XY:

279108

show subpopulations

African (AFR)

AF:

0.0486

AC:

695

AN:

14308

American (AMR)

AF:

0.00589

AC:

150

AN:

25474

Ashkenazi Jewish (ASJ)

AF:

0.0133

AC:

206

AN:

15474

East Asian (EAS)

AF:

0.177

AC:

5616

AN:

31754

South Asian (SAS)

AF:

0.00482

AC:

243

AN:

50412

European-Finnish (FIN)

AF:

0.00691

AC:

216

AN:

31280

Middle Eastern (MID)

AF:

0.00654

AC:

AN:

2598

European-Non Finnish (NFE)

AF:

0.00131

AC:

428

AN:

326516

Other (OTH)

AF:

0.0221

AC:

637

AN:

28856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

387

775

1162

1550

1937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

258

344

430

<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:

0.0239

AC:

3638

AN:

152266

Hom.:

179

Cov.:

AF XY:

0.0244

AC XY:

1815

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0529

AC:

2198

AN:

41548

American (AMR)

AF:

0.0119

AC:

182

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3470

East Asian (EAS)

AF:

0.192

AC:

991

AN:

5164

South Asian (SAS)

AF:

0.00870

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00622

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00106

AC:

AN:

68030

Other (OTH)

AF:

0.0223

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

167

334

501

668

835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0100

Hom.:

178

Bravo

AF:

0.0263

Asia WGS

AF:

0.0840

AC:

291

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.17

(source)

DANN

Benign

0.28

PhyloP100

-1.3

PromoterAI

0.026

Neutral

(source)

Mutation Taster

=100/0

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