Genetic Variant HSPA8:c.-5-145C>T (chr11-123061474-G-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.-5-145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0354 in 661,116 control chromosomes in the GnomAD database, including 2,179 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 0.074 ( 1213 hom., cov: 32)

Exomes 𝑓: 0.024 ( 966 hom. )

Consequence

HSPA8
NM_006597.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.513

Publications

2 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
HSPA8	NM_006597.6 link	c.-5-145C>T	intron_variant	Intron 1 of 8	ENST00000534624.6	NP_006588.1
HSPA8	NM_153201.4 link	c.-5-145C>T	intron_variant	Intron 1 of 7		NP_694881.1
HSPA8	XM_011542798.2 link	c.-5-145C>T	intron_variant	Intron 1 of 8		XP_011541100.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSPA8	ENST00000534624.6 link	c.-5-145C>T		intron_variant	Intron 1 of 8	1	NM_006597.6	ENSP00000432083.1

Frequencies

GnomAD3 genomes

AF:

0.0735

AC:

11182

AN:

152096

Hom.:

1200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0307

Gnomad ASJ

AF:

0.0147

Gnomad EAS

AF:

0.0193

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00288

Gnomad OTH

AF:

0.0512

GnomAD4 exome

AF:

0.0239

AC:

12164

AN:

508902

Hom.:

966

Cov.:

AF XY:

0.0279

AC XY:

7542

AN XY:

270068

show subpopulations

African (AFR)

AF:

0.235

AC:

3244

AN:

13820

American (AMR)

AF:

0.0169

AC:

402

AN:

23790

Ashkenazi Jewish (ASJ)

AF:

0.0126

AC:

189

AN:

15040

East Asian (EAS)

AF:

0.0104

AC:

328

AN:

31668

South Asian (SAS)

AF:

0.127

AC:

6239

AN:

49148

European-Finnish (FIN)

AF:

0.0000324

AC:

AN:

30854

Middle Eastern (MID)

AF:

0.0336

AC:

AN:

2470

European-Non Finnish (NFE)

AF:

0.00252

AC:

791

AN:

313858

Other (OTH)

AF:

0.0314

AC:

887

AN:

28254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

557

1114

1672

2229

2786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<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:

0.0738

AC:

11234

AN:

152214

Hom.:

1213

Cov.:

AF XY:

0.0742

AC XY:

5523

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.231

AC:

9586

AN:

41478

American (AMR)

AF:

0.0306

AC:

468

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0147

AC:

AN:

3472

East Asian (EAS)

AF:

0.0193

AC:

100

AN:

5180

South Asian (SAS)

AF:

0.149

AC:

717

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00287

AC:

195

AN:

68038

Other (OTH)

AF:

0.0507

AC:

107

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

456

912

1367

1823

2279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

240

360

480

600

<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:

0.0443

Hom.:

Bravo

AF:

0.0801

Asia WGS

AF:

0.0980

AC:

339

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.4

(source)

DANN

Benign

0.67

PhyloP100

-0.51

PromoterAI

0.048

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