dbSNP rs441402: HSD17B3:c.454-284G>A (chr9-96250070-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000197.2(HSD17B3):c.454-284G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,386,278 control chromosomes in the GnomAD database, including 48,392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5412 hom., cov: 32)

Exomes 𝑓: 0.26 ( 42980 hom. )

Consequence

HSD17B3
NM_000197.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.42

Publications

0 publications found

Variant links:

Genes affected

HSD17B3 (HGNC:5212): (hydroxysteroid 17-beta dehydrogenase 3) This isoform of 17 beta-hydroxysteroid dehydrogenase is expressed predominantly in the testis and catalyzes the conversion of androstenedione to testosterone. It preferentially uses NADP as cofactor. Deficiency can result in male pseudohermaphroditism with gynecomastia. [provided by RefSeq, Jul 2008]

HSD17B3 links:

ENSG00000285269 (HGNC:):

ENSG00000285269 links:

HSD17B3-AS1 (HGNC:53136): (HSD17B3 antisense RNA 1)

HSD17B3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 9-96250070-C-T is Benign according to our data. Variant chr9-96250070-C-T is described in ClinVar as Benign. ClinVar VariationId is 1251434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000197.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HSD17B3	NM_000197.2	MANE Select	c.454-284G>A	intron	N/A	NP_000188.1	P37058-1
HSD17B3-AS1	NR_146524.1		n.748C>T	non_coding_transcript_exon	Exon 3 of 3
SLC35D2-HSD17B3	NR_182427.1		n.3221-284G>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HSD17B3	ENST00000375263.8	TSL:1 MANE Select	c.454-284G>A	intron	N/A	ENSP00000364412.3	P37058-1
HSD17B3	ENST00000375262.4	TSL:1	c.454-284G>A	intron	N/A	ENSP00000364411.2	P37058-2
ENSG00000285269	ENST00000643789.1		n.*2130-284G>A	intron	N/A	ENSP00000494818.1	A0A2R8Y5X9

Frequencies

GnomAD3 genomes

AF:

0.261

AC:

39580

AN:

151860

Hom.:

5405

Cov.:

show subpopulations

Gnomad AFR

AF:

0.299

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.0285

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.271

Gnomad OTH

AF:

0.255

GnomAD4 exome

AF:

0.258

AC:

318095

AN:

1234300

Hom.:

42980

Cov.:

AF XY:

0.254

AC XY:

151726

AN XY:

596298

show subpopulations

African (AFR)

AF:

0.312

AC:

8591

AN:

27504

American (AMR)

AF:

0.169

AC:

3096

AN:

18360

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

5075

AN:

17676

East Asian (EAS)

AF:

0.0213

AC:

673

AN:

31626

South Asian (SAS)

AF:

0.143

AC:

8329

AN:

58404

European-Finnish (FIN)

AF:

0.279

AC:

6709

AN:

24010

Middle Eastern (MID)

AF:

0.313

AC:

1056

AN:

3378

European-Non Finnish (NFE)

AF:

0.271

AC:

272184

AN:

1002602

Other (OTH)

AF:

0.244

AC:

12382

AN:

50740

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

10584

21169

31753

42338

52922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9660

19320

28980

38640

48300

<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:

0.261

AC:

39621

AN:

151978

Hom.:

5412

Cov.:

AF XY:

0.255

AC XY:

18940

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.299

AC:

12394

AN:

41404

American (AMR)

AF:

0.204

AC:

3113

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

969

AN:

3470

East Asian (EAS)

AF:

0.0286

AC:

148

AN:

5172

South Asian (SAS)

AF:

0.136

AC:

656

AN:

4830

European-Finnish (FIN)

AF:

0.286

AC:

3017

AN:

10542

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.271

AC:

18442

AN:

67960

Other (OTH)

AF:

0.255

AC:

539

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1488

2976

4463

5951

7439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

396

792

1188

1584

1980

<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:

0.266

Hom.:

746

Bravo

AF:

0.256

Asia WGS

AF:

0.109

AC:

378

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.42

(source)

DANN

Benign

0.70

PhyloP100

-2.4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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