dbSNP rs2276075: HSPA8:n.114C>T (chr11-123062094-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.114C>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 0.0642 in 152,844 control chromosomes in the GnomAD database, including 379 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 0.064 ( 376 hom., cov: 33)

Exomes 𝑓: 0.055 ( 3 hom. )

Consequence

HSPA8
ENST00000527983.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.62

Publications

10 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=-0.82).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HSPA8	NM_006597.6 link	c.-36C>T	5_prime_UTR_variant	Exon 1 of 9	ENST00000534624.6	NP_006588.1	P11142-1V9HW22Q53HF2
HSPA8	NM_153201.4 link	c.-36C>T	5_prime_UTR_variant	Exon 1 of 8		NP_694881.1	P11142-2Q53HF2
HSPA8	XM_011542798.2 link	c.-6+253C>T	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.-36C>T		5_prime_UTR_variant	Exon 1 of 9	1	NM_006597.6	ENSP00000432083.1		P11142-1

Frequencies

GnomAD3 genomes

AF:

0.0642

AC:

9763

AN:

152004

Hom.:

376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0549

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.0778

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.0522

Gnomad FIN

AF:

0.0619

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.0513

Gnomad OTH

AF:

0.0638

GnomAD4 exome

AF:

0.0554

AC:

AN:

722

Hom.:

Cov.:

AF XY:

0.0566

AC XY:

AN XY:

548

show subpopulations

African (AFR)

AF:

0.0556

AC:

AN:

American (AMR)

AF:

0.167

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AF:

0.0417

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.167

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0500

AC:

AN:

600

Other (OTH)

AF:

0.0455

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0643

AC:

9775

AN:

152122

Hom.:

376

Cov.:

AF XY:

0.0685

AC XY:

5094

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0549

AC:

2279

AN:

41494

American (AMR)

AF:

0.131

AC:

1996

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0778

AC:

270

AN:

3470

East Asian (EAS)

AF:

0.130

AC:

670

AN:

5164

South Asian (SAS)

AF:

0.0529

AC:

255

AN:

4822

European-Finnish (FIN)

AF:

0.0619

AC:

655

AN:

10574

Middle Eastern (MID)

AF:

0.0788

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0513

AC:

3490

AN:

68012

Other (OTH)

AF:

0.0651

AC:

137

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

465

930

1395

1860

2325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0609

Hom.:

410

Bravo

AF:

0.0707

Asia WGS

AF:

0.0940

AC:

326

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.48

(source)

DANN

Benign

0.72

PhyloP100

-2.6

PromoterAI

-0.098

Neutral

(source)

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over