Variant rs149918713 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_025193.4(HSD3B7):c.975C>T(p.Ala325=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,606,760 control chromosomes in the GnomAD database, including 181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0094 ( 13 hom., cov: 34)

Exomes 𝑓: 0.013 ( 168 hom. )

Consequence

HSD3B7
NM_025193.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.05

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 16-30988048-C-T is Benign according to our data. Variant chr16-30988048-C-T is described in ClinVar as [Benign]. Clinvar id is 261876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.05 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00938 (1429/152356) while in subpopulation NFE AF= 0.0165 (1122/68026). AF 95% confidence interval is 0.0157. There are 13 homozygotes in gnomad4. There are 716 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD3B7	NM_025193.4 linkuse as main transcript	c.975C>T	p.Ala325=	synonymous_variant	7/7	ENST00000297679.10	NP_079469.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD3B7	ENST00000297679.10 linkuse as main transcript	c.975C>T	p.Ala325=	synonymous_variant	7/7	1	NM_025193.4	ENSP00000297679	P1	Q9H2F3-1
	ENST00000624286.1 linkuse as main transcript	n.223G>A		non_coding_transcript_exon_variant	1/1
HSD3B7	ENST00000262520.10 linkuse as main transcript	c.*221C>T		3_prime_UTR_variant	6/6	2		ENSP00000262520		Q9H2F3-2

Frequencies

GnomAD3 genomes

AF:

0.00939

AC:

1429

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00289

Gnomad FIN

AF:

0.0123

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0165

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00907

AC:

2221

AN:

244764

Hom.:

AF XY:

0.00903

AC XY:

1201

AN XY:

132990

show subpopulations

Gnomad AFR exome

AF:

0.00223

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.00269

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00366

Gnomad FIN exome

AF:

0.0109

Gnomad NFE exome

AF:

0.0149

Gnomad OTH exome

AF:

0.0100

GnomAD4 exome

AF:

0.0135

AC:

19594

AN:

1454404

Hom.:

168

Cov.:

AF XY:

0.0130

AC XY:

9429

AN XY:

723942

show subpopulations

Gnomad4 AFR exome

AF:

0.00179

Gnomad4 AMR exome

AF:

0.00398

Gnomad4 ASJ exome

AF:

0.00199

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00366

Gnomad4 FIN exome

AF:

0.0108

Gnomad4 NFE exome

AF:

0.0161

Gnomad4 OTH exome

AF:

0.00966

GnomAD4 genome

AF:

0.00938

AC:

1429

AN:

152356

Hom.:

Cov.:

AF XY:

0.00961

AC XY:

716

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.0123

Gnomad4 NFE

AF:

0.0165

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.0114

Hom.:

Bravo

AF:

0.00866

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.18

DANN

Benign

0.85

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