dbSNP rs11218941: HSPA8:c.-6+363T>C (chr11-123061701-A-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.-6+363T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 280,018 control chromosomes in the GnomAD database, including 10,776 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 ( 7154 hom., cov: 32)

Exomes 𝑓: 0.22 ( 3622 hom. )

Consequence

HSPA8
NM_006597.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.47

Publications

11 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 (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HSPA8	NM_006597.6 link	c.-6+363T>C	intron_variant	Intron 1 of 8	ENST00000534624.6	NP_006588.1	P11142-1V9HW22Q53HF2
HSPA8	NM_153201.4 link	c.-6+363T>C	intron_variant	Intron 1 of 7		NP_694881.1	P11142-2Q53HF2
HSPA8	XM_011542798.2 link	c.-5-372T>C	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.-6+363T>C		intron_variant	Intron 1 of 8	1	NM_006597.6	ENSP00000432083.1		P11142-1

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42407

AN:

151908

Hom.:

7133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.462

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.454

Gnomad SAS

AF:

0.324

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.241

GnomAD4 exome

AF:

0.217

AC:

27793

AN:

127992

Hom.:

3622

Cov.:

AF XY:

0.223

AC XY:

15481

AN XY:

69546

show subpopulations

African (AFR)

AF:

0.468

AC:

1850

AN:

3956

American (AMR)

AF:

0.217

AC:

1109

AN:

5112

Ashkenazi Jewish (ASJ)

AF:

0.154

AC:

476

AN:

3098

East Asian (EAS)

AF:

0.441

AC:

2610

AN:

5916

South Asian (SAS)

AF:

0.285

AC:

6337

AN:

22266

European-Finnish (FIN)

AF:

0.164

AC:

842

AN:

5148

Middle Eastern (MID)

AF:

0.188

AC:

AN:

464

European-Non Finnish (NFE)

AF:

0.174

AC:

13113

AN:

75504

Other (OTH)

AF:

0.210

AC:

1369

AN:

6528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

993

1986

2979

3972

4965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

208

416

624

832

1040

<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:

42486

AN:

152026

Hom.:

7154

Cov.:

AF XY:

0.280

AC XY:

20814

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.463

AC:

19161

AN:

41416

American (AMR)

AF:

0.239

AC:

3655

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

557

AN:

3470

East Asian (EAS)

AF:

0.454

AC:

2340

AN:

5150

South Asian (SAS)

AF:

0.323

AC:

1557

AN:

4818

European-Finnish (FIN)

AF:

0.178

AC:

1880

AN:

10586

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.185

AC:

12579

AN:

67982

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

1466

2931

4397

5862

7328

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:

0.204

Hom.:

5588

Bravo

AF:

0.292

Asia WGS

AF:

0.353

AC:

1226

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

0.91

(source)

DANN

Benign

0.47

PhyloP100

-1.5

PromoterAI

0.047

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

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