dbSNP rs11218942: HSPA8:c.-298G>T (chr11-123063042-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000525624.5(HSPA8):c.-298G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0639 in 152,200 control chromosomes in the GnomAD database, including 371 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 ( 371 hom., cov: 33)

Exomes 𝑓: 0.031 ( 0 hom. )

Consequence

HSPA8
ENST00000525624.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.27

Publications

1 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:

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new If you want to explore the variant's impact on the transcript ENST00000525624.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.76).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000525624.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HSPA8	ENST00000525624.5	TSL:5	c.-298G>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000435154.1	E9PLF4
HSPA8	ENST00000525624.5	TSL:5	c.-298G>T	5_prime_UTR	Exon 1 of 4	ENSP00000435154.1	E9PLF4
ENSG00000288061	ENST00000690490.3		n.550C>A	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0638

AC:

9707

AN:

152050

Hom.:

371

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0563

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.0776

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.0520

Gnomad FIN

AF:

0.0620

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0500

Gnomad OTH

AF:

0.0632

GnomAD4 exome

AF:

0.0313

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0333

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0333

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0639

AC:

9719

AN:

152168

Hom.:

371

Cov.:

AF XY:

0.0682

AC XY:

5071

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0563

AC:

2338

AN:

41524

American (AMR)

AF:

0.130

AC:

1991

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0776

AC:

269

AN:

3468

East Asian (EAS)

AF:

0.126

AC:

648

AN:

5142

South Asian (SAS)

AF:

0.0527

AC:

254

AN:

4824

European-Finnish (FIN)

AF:

0.0620

AC:

657

AN:

10596

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0500

AC:

3403

AN:

68008

Other (OTH)

AF:

0.0644

AC:

136

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

458

916

1374

1832

2290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.0194

Hom.:

Bravo

AF:

0.0727

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.66

(source)

DANN

Benign

0.53

PhyloP100

-1.3

PromoterAI

0.0017

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over