Genetic Variant ENST00000525624.5:c.-75T>C (chr11-123062819-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 ENST00000525624.5(HSPA8):c.-75T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,394 control chromosomes in the GnomAD database, including 1,475 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 0.11 ( 1473 hom., cov: 33)

Exomes 𝑓: 0.056 ( 2 hom. )

Consequence

HSPA8
ENST00000525624.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.441

Publications

4 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=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 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.-75T>C	5_prime_UTR	Exon 1 of 4	ENSP00000435154.1	E9PLF4
ENSG00000288061	ENST00000690490.3		n.327A>G	non_coding_transcript_exon	Exon 1 of 1
ENSG00000288061	ENST00000660892.3		n.59+122A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16351

AN:

151916

Hom.:

1460

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0784

Gnomad ASJ

AF:

0.0303

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.0322

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0427

Gnomad OTH

AF:

0.0822

GnomAD4 exome

AF:

0.0556

AC:

AN:

360

Hom.:

Cov.:

AF XY:

0.0582

AC XY:

AN XY:

292

show subpopulations

African (AFR)

AF:

0.300

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.150

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0430

AC:

AN:

302

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.108

AC:

16403

AN:

152034

Hom.:

1473

Cov.:

AF XY:

0.109

AC XY:

8104

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.235

AC:

9746

AN:

41450

American (AMR)

AF:

0.0785

AC:

1199

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0303

AC:

105

AN:

3468

East Asian (EAS)

AF:

0.193

AC:

993

AN:

5146

South Asian (SAS)

AF:

0.193

AC:

930

AN:

4818

European-Finnish (FIN)

AF:

0.0322

AC:

340

AN:

10574

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0427

AC:

2902

AN:

67978

Other (OTH)

AF:

0.0814

AC:

172

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

688

1377

2065

2754

3442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<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:

0.0636

Hom.:

920

Bravo

AF:

0.115

Asia WGS

AF:

0.165

AC:

571

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.8

(source)

DANN

Benign

0.55

PhyloP100

-0.44

PromoterAI

0.044

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