16-30988113-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025193.4(HSD3B7):c.1040T>C(p.Leu347Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0218 in 1,606,266 control chromosomes in the GnomAD database, including 3,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.090 ( 1864 hom., cov: 34)

Exomes 𝑓: 0.015 ( 1672 hom. )

Consequence

HSD3B7
NM_025193.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.94

Publications

15 publications found

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 Gene-Disease associations (from GenCC):

congenital bile acid synthesis defect 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

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=0.0014500916).

BP6

Variant 16-30988113-T-C is Benign according to our data. Variant chr16-30988113-T-C is described in ClinVar as Benign. ClinVar VariationId is 261869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025193.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HSD3B7	NM_025193.4	MANE Select	c.1040T>C	p.Leu347Pro	missense	Exon 7 of 7	NP_079469.2
HSD3B7	NM_001142777.2		c.*286T>C		3_prime_UTR	Exon 6 of 6	NP_001136249.1
HSD3B7	NM_001142778.2		c.*286T>C		3_prime_UTR	Exon 6 of 6	NP_001136250.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HSD3B7	ENST00000297679.10	TSL:1 MANE Select	c.1040T>C	p.Leu347Pro	missense	Exon 7 of 7	ENSP00000297679.5
ENSG00000279196	ENST00000624286.1	TSL:6	n.158A>G		non_coding_transcript_exon	Exon 1 of 1
HSD3B7	ENST00000262520.10	TSL:2	c.*286T>C		3_prime_UTR	Exon 6 of 6	ENSP00000262520.6

Frequencies

GnomAD3 genomes

AF:

0.0900

AC:

13695

AN:

152194

Hom.:

1858

Cov.:

show subpopulations

Gnomad AFR

AF:

0.298

Gnomad AMI

AF:

0.0462

Gnomad AMR

AF:

0.0392

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00538

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00760

Gnomad OTH

AF:

0.0664

GnomAD2 exomes

AF:

0.0281

AC:

6886

AN:

245154

AF XY:

0.0218

show subpopulations

Gnomad AFR exome

AF:

0.308

Gnomad AMR exome

AF:

0.0203

Gnomad ASJ exome

AF:

0.00728

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.000767

Gnomad NFE exome

AF:

0.00741

Gnomad OTH exome

AF:

0.0176

GnomAD4 exome

AF:

0.0147

AC:

21374

AN:

1453954

Hom.:

1672

Cov.:

AF XY:

0.0137

AC XY:

9877

AN XY:

723110

show subpopulations

African (AFR)

AF:

0.306

AC:

10240

AN:

33410

American (AMR)

AF:

0.0224

AC:

1000

AN:

44642

Ashkenazi Jewish (ASJ)

AF:

0.00797

AC:

208

AN:

26114

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39642

South Asian (SAS)

AF:

0.00675

AC:

582

AN:

86192

European-Finnish (FIN)

AF:

0.000819

AC:

AN:

47614

Middle Eastern (MID)

AF:

0.0283

AC:

163

AN:

5760

European-Non Finnish (NFE)

AF:

0.00688

AC:

7636

AN:

1110320

Other (OTH)

AF:

0.0249

AC:

1503

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1130

2261

3391

4522

5652

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

440

880

1320

1760

2200

<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:

0.0901

AC:

13717

AN:

152312

Hom.:

1864

Cov.:

AF XY:

0.0867

AC XY:

6455

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.297

AC:

12353

AN:

41560

American (AMR)

AF:

0.0391

AC:

599

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.00559

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000753

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00760

AC:

517

AN:

68024

Other (OTH)

AF:

0.0658

AC:

139

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

542

1084

1626

2168

2710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

248

372

496

620

<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:

0.0355

Hom.:

1637

Bravo

AF:

0.103

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.289

AC:

1271

ESP6500EA

AF:

0.00953

AC:

ExAC

AF:

0.0331

AC:

4012

Asia WGS

AF:

0.0290

AC:

101

AN:

3478

EpiCase

AF:

0.00938

EpiControl

AF:

0.0106

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.58

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PhyloP100

1.9

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-5.2

REVEL

Benign

0.23

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0050

Polyphen

0.99

Vest4

0.24

MPC

1.1

ClinPred

0.034

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.78

gMVP

0.97

Mutation Taster

=85/15

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over