dbSNP rs439205: HSD17B8:c.652-69G>A (chr6-33206065-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 NM_014234.5(HSD17B8):c.652-69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,529,484 control chromosomes in the GnomAD database, including 56,354 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 0.28 ( 6797 hom., cov: 31)

Exomes 𝑓: 0.26 ( 49557 hom. )

Consequence

HSD17B8
NM_014234.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.761

Publications

35 publications found

Variant links:

Genes affected

HSD17B8 (HGNC:3554): (hydroxysteroid 17-beta dehydrogenase 8) In mice, the Ke6 protein is a 17-beta-hydroxysteroid dehydrogenase that can regulate the concentration of biologically active estrogens and androgens. It is preferentially an oxidative enzyme and inactivates estradiol, testosterone, and dihydrotestosterone. However, the enzyme has some reductive activity and can synthesize estradiol from estrone. The protein encoded by this gene is similar to Ke6 and is a member of the short-chain dehydrogenase superfamily. An alternatively spliced transcript of this gene has been detected, but the full-length nature of this variant has not been determined. [provided by RefSeq, Jul 2008]

HSD17B8 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=-0.77).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014234.5. 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
	HSD17B8	NM_014234.5	MANE Select	c.652-69G>A		intron	N/A	NP_055049.1	Q92506

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HSD17B8	ENST00000374662.4	TSL:1 MANE Select	c.652-69G>A	intron	N/A	ENSP00000363794.3	Q92506
HSD17B8	ENST00000859230.1		c.679-69G>A	intron	N/A	ENSP00000529289.1
HSD17B8	ENST00000927257.1		c.652-69G>A	intron	N/A	ENSP00000597316.1

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

42970

AN:

151778

Hom.:

6771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.349

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.638

Gnomad SAS

AF:

0.304

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.236

Gnomad OTH

AF:

0.295

GnomAD4 exome

AF:

0.256

AC:

352986

AN:

1377588

Hom.:

49557

Cov.:

AF XY:

0.256

AC XY:

176225

AN XY:

687440

show subpopulations

African (AFR)

AF:

0.336

AC:

10370

AN:

30836

American (AMR)

AF:

0.193

AC:

7738

AN:

40170

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

4543

AN:

24854

East Asian (EAS)

AF:

0.647

AC:

25313

AN:

39102

South Asian (SAS)

AF:

0.296

AC:

24368

AN:

82326

European-Finnish (FIN)

AF:

0.260

AC:

13476

AN:

51824

Middle Eastern (MID)

AF:

0.253

AC:

1397

AN:

5528

European-Non Finnish (NFE)

AF:

0.240

AC:

250548

AN:

1045738

Other (OTH)

AF:

0.266

AC:

15233

AN:

57210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

13894

27788

41682

55576

69470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8734

17468

26202

34936

43670

<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:

0.283

AC:

43043

AN:

151896

Hom.:

6797

Cov.:

AF XY:

0.285

AC XY:

21171

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.350

AC:

14460

AN:

41364

American (AMR)

AF:

0.230

AC:

3510

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

584

AN:

3464

East Asian (EAS)

AF:

0.639

AC:

3296

AN:

5158

South Asian (SAS)

AF:

0.302

AC:

1460

AN:

4832

European-Finnish (FIN)

AF:

0.271

AC:

2854

AN:

10538

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.236

AC:

16044

AN:

67960

Other (OTH)

AF:

0.303

AC:

639

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1556

3112

4668

6224

7780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.251

Hom.:

14671

Bravo

AF:

0.288

Asia WGS

AF:

0.390

AC:

1352

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.9

(source)

DANN

Benign

0.71

PhyloP100

-0.76

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over