rs6201

chr1-119511592-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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, single submitter B:1

Conservation

PhyloP100: 2.33

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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 id is 1222205.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
HSD3B1	NM_000862.3 linkuse as main transcript	c.235A>G	p.Ile79Val	missense_variant	3/4	ENST00000369413.8
HSD3B1	NM_001328615.1 linkuse as main transcript	c.235A>G	p.Ile79Val	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
HSD3B1	ENST00000369413.8 linkuse as main transcript	c.235A>G	p.Ile79Val	missense_variant	3/4	1	NM_000862.3	P1
HSD3B1	ENST00000528909.1 linkuse as main transcript	c.235A>G	p.Ile79Val	missense_variant	2/3	1		P1
HSD3B1	ENST00000531340.5 linkuse as main transcript	c.235A>G	p.Ile79Val	missense_variant	3/3	3
HSD3B1	ENST00000492140.1 linkuse as main transcript	n.370A>G		non_coding_transcript_exon_variant	3/3	2

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

GnomAD3 exomes

AF:

0.0426

AC:

10670

AN:

250476

Hom.:

1124

AF XY:

0.0361

AC XY:

4886

AN XY:

135402

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 SAS exome

AF:

0.0524

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

Gnomad4 AFR exome

AF:

0.352

Gnomad4 AMR exome

AF:

0.0709

Gnomad4 ASJ exome

AF:

0.00459

Gnomad4 EAS exome

AF:

0.0258

Gnomad4 SAS exome

AF:

0.0553

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00186

Gnomad4 OTH exome

AF:

0.0353

GnomAD4 genome

AF:

0.100

AC:

15276

AN:

152112

Hom.:

2307

Cov.:

AF XY:

0.0977

AC XY:

7269

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.328

Gnomad4 AMR

AF:

0.0566

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.0421

Gnomad4 SAS

AF:

0.0535

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00251

Gnomad4 OTH

AF:

0.0753

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:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 13, 2018

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

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

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

MutationTaster

Benign

1.0

P;P;P

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over