dbSNP rs6201: HSD3B1:p.Ile79Val (chr1-119511592-A-G) – 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_000862.3(HSD3B1):c.235A>G(p.Ile79Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0251 in 1,613,244 control chromosomes in the GnomAD database, including 4,875 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 2307 hom., cov: 31)

Exomes 𝑓: 0.017 ( 2568 hom. )

Consequence

HSD3B1
NM_000862.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.33

Publications

10 publications found

Variant links:

Genes affected

HSD3B1 (HGNC:5217): (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1) The protein encoded by this gene is an enzyme that catalyzes the oxidative conversion of delta-5-3-beta-hydroxysteroid precursors into delta-4-ketosteroids, which leads to the production of all classes of steroid hormones. The encoded protein also catalyzes the interconversion of 3-beta-hydroxy- and 3-keto-5-alpha-androstane steroids. [provided by RefSeq, Jun 2016]

HSD3B1 links:

ENSG00000293080 (HGNC:):

ENSG00000293080 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 (MetaRNN=0.0058858395).

BP6

Variant 1-119511592-A-G is Benign according to our data. Variant chr1-119511592-A-G is described in ClinVar as Benign. ClinVar VariationId is 1222205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD3B1	NM_000862.3 link	c.235A>G	p.Ile79Val	missense_variant	Exon 3 of 4	ENST00000369413.8	NP_000853.1
HSD3B1	NM_001328615.1 link	c.235A>G	p.Ile79Val	missense_variant	Exon 3 of 4		NP_001315544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD3B1	ENST00000369413.8 link	c.235A>G	p.Ile79Val	missense_variant	Exon 3 of 4	1	NM_000862.3	ENSP00000358421.3

Frequencies

GnomAD3 genomes

AF:

0.100

AC:

15216

AN:

151994

Hom.:

2292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0566

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.0420

Gnomad SAS

AF:

0.0537

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.00251

Gnomad OTH

AF:

0.0751

GnomAD2 exomes

AF:

0.0426

AC:

10670

AN:

250476

AF XY:

0.0361

show subpopulations

Gnomad AFR exome

AF:

0.335

Gnomad AMR exome

AF:

0.0718

Gnomad ASJ exome

AF:

0.00447

Gnomad EAS exome

AF:

0.0397

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00256

Gnomad OTH exome

AF:

0.0262

GnomAD4 exome

AF:

0.0173

AC:

25209

AN:

1461132

Hom.:

2568

Cov.:

AF XY:

0.0171

AC XY:

12426

AN XY:

726884

show subpopulations

African (AFR)

AF:

0.352

AC:

11715

AN:

33304

American (AMR)

AF:

0.0709

AC:

3167

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00459

AC:

120

AN:

26128

East Asian (EAS)

AF:

0.0258

AC:

1024

AN:

39682

South Asian (SAS)

AF:

0.0553

AC:

4767

AN:

86154

European-Finnish (FIN)

AF:

0.000225

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.0351

AC:

202

AN:

5760

European-Non Finnish (NFE)

AF:

0.00186

AC:

2071

AN:

1111670

Other (OTH)

AF:

0.0353

AC:

2131

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.409

Heterozygous variant carriers

1038

2076

3115

4153

5191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

478

956

1434

1912

2390

<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:

0.100

AC:

15276

AN:

152112

Hom.:

2307

Cov.:

AF XY:

0.0977

AC XY:

7269

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.328

AC:

13565

AN:

41390

American (AMR)

AF:

0.0566

AC:

866

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00663

AC:

AN:

3470

East Asian (EAS)

AF:

0.0421

AC:

218

AN:

5178

South Asian (SAS)

AF:

0.0535

AC:

258

AN:

4818

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00251

AC:

171

AN:

68016

Other (OTH)

AF:

0.0753

AC:

159

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

559

1118

1676

2235

2794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<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:

0.0476

Hom.:

511

Bravo

AF:

0.116

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.316

AC:

1391

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.0484

AC:

5874

EpiCase

AF:

0.00365

EpiControl

AF:

0.00391

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 25363768) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

1.3

(source)

DANN

Benign

0.17

DEOGEN2

Benign

0.22

T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.46

T;.;T

MetaRNN

Benign

0.0059

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.6

.;N;N

PhyloP100

2.3

PrimateAI

Benign

0.29

PROVEAN

Benign

0.70

N;N;N

REVEL

Benign

0.21

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.074

MPC

0.024

ClinPred

0.0074

GERP RS

0.15

Varity_R

0.041

gMVP

0.14

Mutation Taster

=99/1

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