Genetic Variant HSD3B1:p.Arg71Ile (chr1-119511569-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000862.3(HSD3B1):c.212G>T(p.Arg71Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00679 in 1,613,798 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 3 hom., cov: 31)

Exomes 𝑓: 0.0070 ( 39 hom. )

Consequence

HSD3B1
NM_000862.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0340

Publications

11 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014194846).

BP6

Variant 1-119511569-G-T is Benign according to our data. Variant chr1-119511569-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3387985.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD3B1	NM_000862.3 link	c.212G>T	p.Arg71Ile	missense_variant	Exon 3 of 4	ENST00000369413.8	NP_000853.1
HSD3B1	NM_001328615.1 link	c.212G>T	p.Arg71Ile	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.212G>T	p.Arg71Ile	missense_variant	Exon 3 of 4	1	NM_000862.3	ENSP00000358421.3

Frequencies

GnomAD3 genomes

AF:

0.00464

AC:

706

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00438

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00794

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00409

AC:

1025

AN:

250902

AF XY:

0.00422

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00229

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00129

Gnomad NFE exome

AF:

0.00716

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00702

AC:

10257

AN:

1461534

Hom.:

Cov.:

AF XY:

0.00685

AC XY:

4978

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

33468

American (AMR)

AF:

0.00244

AC:

109

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39680

South Asian (SAS)

AF:

0.00160

AC:

138

AN:

86248

European-Finnish (FIN)

AF:

0.00159

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00855

AC:

9504

AN:

1111750

Other (OTH)

AF:

0.00578

AC:

349

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

513

1026

1540

2053

2566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

368

736

1104

1472

1840

<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:

0.00464

AC:

706

AN:

152264

Hom.:

Cov.:

AF XY:

0.00428

AC XY:

319

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

41554

American (AMR)

AF:

0.00438

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00208

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00141

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00794

AC:

540

AN:

68024

Other (OTH)

AF:

0.00427

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

103

137

171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00606

Hom.:

Bravo

AF:

0.00436

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00849

AC:

ExAC

AF:

0.00393

AC:

477

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00714

EpiControl

AF:

0.00711

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

HSD3B1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Uncertain

0.62

D;D;D

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.12

LIST_S2

Uncertain

0.91

D;.;D

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Uncertain

0.21

MutationAssessor

Pathogenic

3.5

.;M;M

PhyloP100

0.034

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-5.9

D;D;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

0.93

.;P;P

Vest4

0.56

MVP

0.92

MPC

0.16

ClinPred

0.091

GERP RS

0.84

Varity_R

0.38

gMVP

0.20

Mutation Taster

=100/0

polymorphism

(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