dbSNP rs12809466: HSD17B6:c.-19-108A>G (chr12-56773726-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 NM_003725.4(HSD17B6):c.-19-108A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0691 in 1,069,036 control chromosomes in the GnomAD database, including 2,848 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 0.080 ( 535 hom., cov: 32)

Exomes 𝑓: 0.067 ( 2313 hom. )

Consequence

HSD17B6
NM_003725.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.536

Publications

3 publications found

Variant links:

Genes affected

HSD17B6 (HGNC:23316): (hydroxysteroid 17-beta dehydrogenase 6) The protein encoded by this gene has both oxidoreductase and epimerase activities and is involved in androgen catabolism. The oxidoreductase activity can convert 3 alpha-adiol to dihydrotestosterone, while the epimerase activity can convert androsterone to epi-androsterone. Both reactions use NAD+ as the preferred cofactor. This gene is a member of the retinol dehydrogenase family. [provided by RefSeq, Aug 2013]

HSD17B6 links:

ENSG00000309589 (HGNC:):

ENSG00000309589 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003725.4. 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
	HSD17B6	NM_003725.4	MANE Select	c.-19-108A>G		intron	N/A	NP_003716.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HSD17B6	ENST00000322165.1	TSL:1 MANE Select	c.-19-108A>G	intron	N/A	ENSP00000318631.1	O14756
HSD17B6	ENST00000859685.1		c.-127A>G	5_prime_UTR	Exon 1 of 4	ENSP00000529744.1
HSD17B6	ENST00000859675.1		c.-19-108A>G	intron	N/A	ENSP00000529734.1

Frequencies

GnomAD3 genomes

AF:

0.0800

AC:

12169

AN:

152178

Hom.:

534

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0658

Gnomad ASJ

AF:

0.0629

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0290

Gnomad FIN

AF:

0.0779

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0751

Gnomad OTH

AF:

0.0769

GnomAD4 exome

AF:

0.0672

AC:

61650

AN:

916740

Hom.:

2313

AF XY:

0.0662

AC XY:

29947

AN XY:

452414

show subpopulations

African (AFR)

AF:

0.117

AC:

2488

AN:

21230

American (AMR)

AF:

0.0530

AC:

939

AN:

17728

Ashkenazi Jewish (ASJ)

AF:

0.0561

AC:

896

AN:

15982

East Asian (EAS)

AF:

0.000123

AC:

AN:

32578

South Asian (SAS)

AF:

0.0322

AC:

1473

AN:

45698

European-Finnish (FIN)

AF:

0.0756

AC:

2708

AN:

35810

Middle Eastern (MID)

AF:

0.0710

AC:

205

AN:

2886

European-Non Finnish (NFE)

AF:

0.0716

AC:

50406

AN:

704050

Other (OTH)

AF:

0.0621

AC:

2531

AN:

40778

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

2760

5520

8280

11040

13800

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1716

3432

5148

6864

8580

<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:

0.0799

AC:

12176

AN:

152296

Hom.:

535

Cov.:

AF XY:

0.0796

AC XY:

5924

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.112

AC:

4670

AN:

41564

American (AMR)

AF:

0.0656

AC:

1004

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0629

AC:

218

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5192

South Asian (SAS)

AF:

0.0294

AC:

142

AN:

4824

European-Finnish (FIN)

AF:

0.0779

AC:

827

AN:

10610

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0751

AC:

5105

AN:

68020

Other (OTH)

AF:

0.0756

AC:

160

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

569

1138

1708

2277

2846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<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:

0.0770

Hom.:

Bravo

AF:

0.0796

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.96

(source)

DANN

Benign

0.71

PhyloP100

-0.54

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