dbSNP rs1136141: HSPA8:n.139C>T (chr11-123062069-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 ENST00000527983.5(HSPA8):n.139C>T 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 0.143 in 152,516 control chromosomes in the GnomAD database, including 1,587 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 ( 1581 hom., cov: 33)

Exomes 𝑓: 0.13 ( 6 hom. )

Consequence

HSPA8
ENST00000527983.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.469

Publications

21 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=-0.78).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
HSPA8	NM_006597.6 link	c.-11C>T	5_prime_UTR_variant	Exon 1 of 9	ENST00000534624.6	NP_006588.1
HSPA8	NM_153201.4 link	c.-11C>T	5_prime_UTR_variant	Exon 1 of 8		NP_694881.1
HSPA8	XM_011542798.2 link	c.-6+278C>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.-11C>T		5_prime_UTR_variant	Exon 1 of 9	1	NM_006597.6	ENSP00000432083.1

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21712

AN:

151982

Hom.:

1581

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.205

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.0688

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.137

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.137

GnomAD4 exome

AF:

0.128

AC:

AN:

414

Hom.:

Cov.:

AF XY:

0.114

AC XY:

AN XY:

290

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0600

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.150

AC:

AN:

326

Other (OTH)

AF:

0.0714

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.143

AC:

21726

AN:

152102

Hom.:

1581

Cov.:

AF XY:

0.142

AC XY:

10550

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.158

AC:

6554

AN:

41500

American (AMR)

AF:

0.147

AC:

2240

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

416

AN:

3468

East Asian (EAS)

AF:

0.0691

AC:

357

AN:

5166

South Asian (SAS)

AF:

0.121

AC:

582

AN:

4826

European-Finnish (FIN)

AF:

0.139

AC:

1470

AN:

10576

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.141

AC:

9598

AN:

67984

Other (OTH)

AF:

0.134

AC:

283

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

971

1943

2914

3886

4857

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

232

464

696

928

1160

<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:

0.140

Hom.:

4320

Bravo

AF:

0.145

Asia WGS

AF:

0.0960

AC:

332

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.4

(source)

DANN

Benign

0.66

PhyloP100

-0.47

PromoterAI

0.0028

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Mutation Taster

=300/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over