Genetic Variant HSPA8:c.1756-7T>A (chr11-123057926-A-T) – 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.1756-7T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0234 in 1,588,350 control chromosomes in the GnomAD database, including 1,028 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.021 ( 101 hom., cov: 32)

Exomes 𝑓: 0.024 ( 927 hom. )

Consequence

HSPA8
NM_006597.6 splice_region, intron

Scores

Splicing: ADA: 0.0001606

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0280

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:

SNORD14E (HGNC:30354): (small nucleolar RNA, C/D box 14E)

SNORD14E 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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HSPA8	NM_006597.6 link	c.1756-7T>A	splice_region_variant, intron_variant	Intron 8 of 8	ENST00000534624.6	NP_006588.1	P11142-1V9HW22Q53HF2
HSPA8	NM_153201.4 link	c.1388-98T>A	intron_variant	Intron 7 of 7		NP_694881.1	P11142-2Q53HF2
HSPA8	XM_011542798.2 link	c.1756-7T>A	splice_region_variant, intron_variant	Intron 8 of 8		XP_011541100.1	P11142-1V9HW22
SNORD14E	NR_003125.2 link	n.*151T>A	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA8	ENST00000534624.6 link	c.1756-7T>A		splice_region_variant, intron_variant	Intron 8 of 8	1	NM_006597.6	ENSP00000432083.1		P11142-1

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3158

AN:

152132

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00391

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0301

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.171

Gnomad SAS

AF:

0.0435

Gnomad FIN

AF:

0.0174

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0177

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.0369

AC:

8339

AN:

225842

AF XY:

0.0359

show subpopulations

Gnomad AFR exome

AF:

0.00387

Gnomad AMR exome

AF:

0.0591

Gnomad ASJ exome

AF:

0.00700

Gnomad EAS exome

AF:

0.172

Gnomad FIN exome

AF:

0.0198

Gnomad NFE exome

AF:

0.0166

Gnomad OTH exome

AF:

0.0224

GnomAD4 exome

AF:

0.0237

AC:

33980

AN:

1436100

Hom.:

927

Cov.:

AF XY:

0.0241

AC XY:

17233

AN XY:

713834

show subpopulations

African (AFR)

AF:

0.00264

AC:

AN:

32150

American (AMR)

AF:

0.0549

AC:

2126

AN:

38744

Ashkenazi Jewish (ASJ)

AF:

0.00573

AC:

141

AN:

24622

East Asian (EAS)

AF:

0.165

AC:

6528

AN:

39450

South Asian (SAS)

AF:

0.0458

AC:

3793

AN:

82738

European-Finnish (FIN)

AF:

0.0188

AC:

996

AN:

53050

Middle Eastern (MID)

AF:

0.00532

AC:

AN:

5636

European-Non Finnish (NFE)

AF:

0.0172

AC:

18926

AN:

1100486

Other (OTH)

AF:

0.0229

AC:

1355

AN:

59224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

1445

2889

4334

5778

7223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

838

1676

2514

3352

4190

<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:

0.0207

AC:

3159

AN:

152250

Hom.:

101

Cov.:

AF XY:

0.0223

AC XY:

1658

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.00390

AC:

162

AN:

41558

American (AMR)

AF:

0.0303

AC:

463

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00691

AC:

AN:

3472

East Asian (EAS)

AF:

0.171

AC:

884

AN:

5174

South Asian (SAS)

AF:

0.0439

AC:

212

AN:

4824

European-Finnish (FIN)

AF:

0.0174

AC:

185

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0176

AC:

1200

AN:

68012

Other (OTH)

AF:

0.0133

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

154

309

463

618

772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0154

Hom.:

Bravo

AF:

0.0216

Asia WGS

AF:

0.0650

AC:

227

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.18

(source)

DANN

Benign

0.67

PhyloP100

-0.028

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00016

dbscSNV1_RF

Benign

0.010

SpliceAI score (max)

0.020

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