dbSNP rs2066475: HSD17B3:c.278-67G>A (chr9-96252977-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.278-67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 941,622 control chromosomes in the GnomAD database, including 29,845 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5221 hom., cov: 31)

Exomes 𝑓: 0.24 ( 24624 hom. )

Consequence

HSD17B3
NM_000197.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.233

Publications

3 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=-0.79).

BP6

Variant 9-96252977-C-T is Benign according to our data. Variant chr9-96252977-C-T is described in ClinVar as Benign. ClinVar VariationId is 1255201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2 link	c.278-67G>A		intron_variant	Intron 3 of 10	ENST00000375263.8	NP_000188.1	P37058-1Q6FH62
SLC35D2-HSD17B3	NR_182427.1 link	n.3045-67G>A		intron_variant	Intron 18 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8 link	c.278-67G>A		intron_variant	Intron 3 of 10	1	NM_000197.2	ENSP00000364412.3		P37058-1
ENSG00000285269	ENST00000643789.1 link	n.*1954-67G>A		intron_variant	Intron 14 of 21			ENSP00000494818.1		A0A2R8Y5X9

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38781

AN:

151666

Hom.:

5217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.309

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.0273

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.273

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.244

GnomAD4 exome

AF:

0.239

AC:

188974

AN:

789838

Hom.:

24624

AF XY:

0.235

AC XY:

98723

AN XY:

419552

show subpopulations

African (AFR)

AF:

0.301

AC:

6243

AN:

20740

American (AMR)

AF:

0.129

AC:

5662

AN:

43878

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

6148

AN:

21994

East Asian (EAS)

AF:

0.0216

AC:

791

AN:

36680

South Asian (SAS)

AF:

0.142

AC:

10365

AN:

72840

European-Finnish (FIN)

AF:

0.266

AC:

13560

AN:

51004

Middle Eastern (MID)

AF:

0.347

AC:

1550

AN:

4466

European-Non Finnish (NFE)

AF:

0.271

AC:

135244

AN:

499948

Other (OTH)

AF:

0.246

AC:

9411

AN:

38288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

7828

15655

23483

31310

39138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2338

4676

7014

9352

11690

<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:

0.256

AC:

38813

AN:

151784

Hom.:

5221

Cov.:

AF XY:

0.249

AC XY:

18492

AN XY:

74148

show subpopulations

African (AFR)

AF:

0.297

AC:

12267

AN:

41332

American (AMR)

AF:

0.195

AC:

2971

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

947

AN:

3468

East Asian (EAS)

AF:

0.0273

AC:

141

AN:

5162

South Asian (SAS)

AF:

0.131

AC:

628

AN:

4800

European-Finnish (FIN)

AF:

0.273

AC:

2868

AN:

10518

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.266

AC:

18106

AN:

67944

Other (OTH)

AF:

0.245

AC:

516

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1456

2911

4367

5822

7278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<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:

0.260

Hom.:

692

Bravo

AF:

0.252

Asia WGS

AF:

0.101

AC:

351

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 08, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.4

(source)

DANN

Benign

0.73

PhyloP100

-0.23

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over