dbSNP rs2236658: HSPA8:n.246A>G (chr11-123062424-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000532780.5(HSPA8):n.246A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,272 control chromosomes in the GnomAD database, including 2,566 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 0.14 ( 2566 hom., cov: 33)

Exomes 𝑓: 0.020 ( 0 hom. )

Consequence

HSPA8
ENST00000532780.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.660

Publications

6 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:

ENSG00000288061 (HGNC:):

ENSG00000288061 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=-0.6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSPA8	XM_011542798.2 link	c.-83A>G		5_prime_UTR_variant	Exon 1 of 9		XP_011541100.1	P11142-1V9HW22
LOC124902775	XR_007062927.1 link	n.-238T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
HSPA8	ENST00000532780.5 link	n.246A>G	non_coding_transcript_exon_variant	Exon 1 of 4	2
ENSG00000288061	ENST00000836650.1 link	n.127T>C	non_coding_transcript_exon_variant	Exon 1 of 2
HSPA8	ENST00000525624.5 link	c.-6+326A>G	intron_variant	Intron 1 of 3	5	ENSP00000435154.1	E9PLF4

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20587

AN:

152002

Hom.:

2549

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0919

Gnomad ASJ

AF:

0.0406

Gnomad EAS

AF:

0.389

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.0385

Gnomad MID

AF:

0.0541

Gnomad NFE

AF:

0.0438

Gnomad OTH

AF:

0.104

GnomAD4 exome

AF:

0.0197

AC:

AN:

152

Hom.:

Cov.:

AF XY:

0.0238

AC XY:

AN XY:

126

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0259

AC:

AN:

116

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.136

AC:

20652

AN:

152120

Hom.:

2566

Cov.:

AF XY:

0.137

AC XY:

10218

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.301

AC:

12498

AN:

41494

American (AMR)

AF:

0.0921

AC:

1409

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0406

AC:

141

AN:

3470

East Asian (EAS)

AF:

0.389

AC:

1996

AN:

5136

South Asian (SAS)

AF:

0.203

AC:

980

AN:

4822

European-Finnish (FIN)

AF:

0.0385

AC:

408

AN:

10590

Middle Eastern (MID)

AF:

0.0616

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0438

AC:

2976

AN:

67996

Other (OTH)

AF:

0.106

AC:

223

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

823

1645

2468

3290

4113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<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:

0.102

Hom.:

221

Bravo

AF:

0.146

Asia WGS

AF:

0.259

AC:

897

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

0.66

PromoterAI

0.023

Neutral

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over