chr16-30985729-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_025193.4(HSD3B7):c.71A>G(p.His24Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0025 in 1,608,688 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H24Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0015 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 116 hom. )

Consequence

HSD3B7
NM_025193.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.13

Variant links:

Genes affected

HSD3B7 (HGNC:18324): (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7) This gene encodes an enzyme which is involved in the initial stages of the synthesis of bile acids from cholesterol and a member of the short-chain dehydrogenase/reductase superfamily. The encoded protein is a membrane-associated endoplasmic reticulum protein which is active against 7-alpha hydrosylated sterol substrates. Mutations in this gene are associated with a congenital bile acid synthesis defect which leads to neonatal cholestasis, a form of progressive liver disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

HSD3B7 links:

ENSG00000279196 (HGNC:):

ENSG00000279196 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=0.0062257946).

BP6

Variant 16-30985729-A-G is Benign according to our data. Variant chr16-30985729-A-G is described in ClinVar as [Benign]. Clinvar id is 284323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-30985729-A-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00152 (232/152382) while in subpopulation SAS AF = 0.0466 (225/4832). AF 95% confidence interval is 0.0416. There are 6 homozygotes in GnomAd4. There are 160 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD3B7	NM_025193.4 link	c.71A>G	p.His24Arg	missense_variant	Exon 2 of 7	ENST00000297679.10	NP_079469.2	Q9H2F3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD3B7	ENST00000297679.10 link	c.71A>G	p.His24Arg	missense_variant	Exon 2 of 7	1	NM_025193.4	ENSP00000297679.5		Q9H2F3-1

Frequencies

GnomAD3 genomes

AF:

0.00153

AC:

233

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0467

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00519

AC:

1238

AN:

238478

AF XY:

0.00706

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000296

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000467

Gnomad OTH exome

AF:

0.00205

GnomAD4 exome

AF:

0.00260

AC:

3788

AN:

1456306

Hom.:

116

Cov.:

AF XY:

0.00379

AC XY:

2742

AN XY:

724224

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33392

American (AMR)

AF:

0.0000678

AC:

AN:

44250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25990

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39644

South Asian (SAS)

AF:

0.0422

AC:

3604

AN:

85318

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52170

Middle Eastern (MID)

AF:

0.00157

AC:

AN:

4468

European-Non Finnish (NFE)

AF:

0.0000324

AC:

AN:

1110954

Other (OTH)

AF:

0.00220

AC:

132

AN:

60120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

268

536

805

1073

1341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00152

AC:

232

AN:

152382

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

160

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.0000721

AC:

AN:

41600

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.0466

AC:

225

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68040

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000555

Hom.:

Bravo

AF:

0.000348

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00598

AC:

726

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 30, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Nov 26, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.090

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.67

.;D;D;.

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

D;D;T;D

MetaRNN

Benign

0.0062

T;T;T;T

MetaSVM

Uncertain

0.38

MutationAssessor

Benign

1.8

L;L;.;.

PhyloP100

2.1

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.6

D;D;.;.

REVEL

Pathogenic

0.67

Sift

Benign

0.20

T;T;.;.

Sift4G

Benign

0.60

T;T;T;T

Polyphen

0.99

.;D;.;.

Vest4

0.67

MVP

0.92

MPC

0.92

ClinPred

0.054

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.53

gMVP

0.89

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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chr16-30985729-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over