16-30987821-A-G

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.748A>G(p.Thr250Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 1,612,980 control chromosomes in the GnomAD database, including 303,549 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 (★★).

Frequency

Genomes: 𝑓 0.53 ( 23619 hom., cov: 34)

Exomes 𝑓: 0.61 ( 279930 hom. )

Consequence

HSD3B7
NM_025193.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.602

Publications

59 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, Labcorp Genetics (formerly Invitae), G2P

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=9.0653583E-7).

BP6

Variant 16-30987821-A-G is Benign according to our data. Variant chr16-30987821-A-G is described in ClinVar as Benign. ClinVar VariationId is 261873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 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	UniProt
HSD3B7	NM_025193.4	MANE Select	c.748A>G	p.Thr250Ala	missense	Exon 7 of 7	NP_079469.2
HSD3B7	NM_001142777.2		c.585A>G	p.Gln195Gln	synonymous	Exon 6 of 6	NP_001136249.1	Q9H2F3-2
HSD3B7	NM_001142778.2		c.585A>G	p.Gln195Gln	synonymous	Exon 6 of 6	NP_001136250.1	Q9H2F3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HSD3B7	ENST00000297679.10	TSL:1 MANE Select	c.748A>G	p.Thr250Ala	missense	Exon 7 of 7	ENSP00000297679.5	Q9H2F3-1
HSD3B7	ENST00000867909.1		c.871A>G	p.Thr291Ala	missense	Exon 7 of 7	ENSP00000537968.1
HSD3B7	ENST00000867910.1		c.871A>G	p.Thr291Ala	missense	Exon 7 of 7	ENSP00000537969.1

Frequencies

GnomAD3 genomes

AF:

0.530

AC:

80523

AN:

152056

Hom.:

23603

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.631

Gnomad AMR

AF:

0.571

Gnomad ASJ

AF:

0.690

Gnomad EAS

AF:

0.905

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.668

Gnomad MID

AF:

0.737

Gnomad NFE

AF:

0.626

Gnomad OTH

AF:

0.593

GnomAD2 exomes

AF:

0.585

AC:

146027

AN:

249454

AF XY:

0.579

show subpopulations

Gnomad AFR exome

AF:

0.261

Gnomad AMR exome

AF:

0.561

Gnomad ASJ exome

AF:

0.673

Gnomad EAS exome

AF:

0.911

Gnomad FIN exome

AF:

0.657

Gnomad NFE exome

AF:

0.634

Gnomad OTH exome

AF:

0.609

GnomAD4 exome

AF:

0.610

AC:

890708

AN:

1460806

Hom.:

279930

Cov.:

AF XY:

0.604

AC XY:

438775

AN XY:

726750

show subpopulations

African (AFR)

AF:

0.265

AC:

8878

AN:

33478

American (AMR)

AF:

0.565

AC:

25254

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.673

AC:

17572

AN:

26128

East Asian (EAS)

AF:

0.910

AC:

36122

AN:

39696

South Asian (SAS)

AF:

0.332

AC:

28670

AN:

86254

European-Finnish (FIN)

AF:

0.654

AC:

34315

AN:

52458

Middle Eastern (MID)

AF:

0.699

AC:

4033

AN:

5766

European-Non Finnish (NFE)

AF:

0.629

AC:

699076

AN:

1111922

Other (OTH)

AF:

0.609

AC:

36788

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

20932

41863

62795

83726

104658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18454

36908

55362

73816

92270

<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:

0.530

AC:

80584

AN:

152174

Hom.:

23619

Cov.:

AF XY:

0.531

AC XY:

39478

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.280

AC:

11616

AN:

41506

American (AMR)

AF:

0.571

AC:

8728

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.690

AC:

2396

AN:

3470

East Asian (EAS)

AF:

0.906

AC:

4679

AN:

5166

South Asian (SAS)

AF:

0.310

AC:

1496

AN:

4826

European-Finnish (FIN)

AF:

0.668

AC:

7088

AN:

10610

Middle Eastern (MID)

AF:

0.741

AC:

218

AN:

294

European-Non Finnish (NFE)

AF:

0.626

AC:

42544

AN:

67984

Other (OTH)

AF:

0.590

AC:

1246

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1819

3639

5458

7278

9097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

680

1360

2040

2720

3400

<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:

0.595

Hom.:

42813

Bravo

AF:

0.521

TwinsUK

AF:

0.622

AC:

2306

ALSPAC

AF:

0.628

AC:

2421

ESP6500AA

AF:

0.289

AC:

1271

ESP6500EA

AF:

0.642

AC:

5518

ExAC

AF:

0.572

AC:

69382

Asia WGS

AF:

0.547

AC:

1908

AN:

3478

EpiCase

AF:

0.635

EpiControl

AF:

0.644

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

Congenital bile acid synthesis defect 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.4

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.23

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0075

LIST_S2

Benign

0.034

MetaRNN

Benign

9.1e-7

MetaSVM

Benign

-0.97

PhyloP100

-0.60

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.13

REVEL

Benign

0.076

Sift

Benign

0.48

Sift4G

Benign

0.79

Polyphen

0.0

Vest4

0.0040

MPC

0.27

ClinPred

0.0092

GERP RS

0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.037

gMVP

0.46

Mutation Taster

=100/0

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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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

Computational scores

Splicing

Publications

Other links and lift over