Variant chr16-30988141-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_025193.4(HSD3B7):c.1068T>C(p.Arg356Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 1,605,016 control chromosomes in the GnomAD database, including 302,080 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 23616 hom., cov: 33)

Exomes 𝑓: 0.61 ( 278464 hom. )

Consequence

HSD3B7
NM_025193.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.85

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 16-30988141-T-C is Benign according to our data. Variant chr16-30988141-T-C is described in ClinVar as [Benign]. Clinvar id is 261870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-30988141-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.86 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD3B7	NM_025193.4 linkuse as main transcript	c.1068T>C	p.Arg356Arg	synonymous_variant	7/7	ENST00000297679.10	NP_079469.2	Q9H2F3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HSD3B7	ENST00000297679.10 linkuse as main transcript	c.1068T>C	p.Arg356Arg	synonymous_variant	7/7	1	NM_025193.4	ENSP00000297679.5	Q9H2F3-1
HSD3B7	ENST00000262520.10 linkuse as main transcript	c.*314T>C		3_prime_UTR_variant	6/6	2		ENSP00000262520.6	Q9H2F3-2
ENSG00000279196	ENST00000624286.1 linkuse as main transcript	n.130A>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

AF:

0.529

AC:

80507

AN:

152070

Hom.:

23600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.278

Gnomad AMI

AF:

0.630

Gnomad AMR

AF:

0.571

Gnomad ASJ

AF:

0.690

Gnomad EAS

AF:

0.906

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

GnomAD3 exomes

AF:

0.587

AC:

141223

AN:

240682

Hom.:

44486

AF XY:

0.581

AC XY:

75975

AN XY:

130876

show subpopulations

Gnomad AFR exome

AF:

0.263

Gnomad AMR exome

AF:

0.564

Gnomad ASJ exome

AF:

0.674

Gnomad EAS exome

AF:

0.910

Gnomad SAS exome

AF:

0.325

Gnomad FIN exome

AF:

0.659

Gnomad NFE exome

AF:

0.638

Gnomad OTH exome

AF:

0.611

GnomAD4 exome

AF:

0.610

AC:

886154

AN:

1452828

Hom.:

278464

Cov.:

AF XY:

0.604

AC XY:

436546

AN XY:

722678

show subpopulations

Gnomad4 AFR exome

AF:

0.265

Gnomad4 AMR exome

AF:

0.567

Gnomad4 ASJ exome

AF:

0.673

Gnomad4 EAS exome

AF:

0.910

Gnomad4 SAS exome

AF:

0.333

Gnomad4 FIN exome

AF:

0.654

Gnomad4 NFE exome

AF:

0.629

Gnomad4 OTH exome

AF:

0.610

GnomAD4 genome

AF:

0.529

AC:

80568

AN:

152188

Hom.:

23616

Cov.:

AF XY:

0.531

AC XY:

39477

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.279

Gnomad4 AMR

AF:

0.571

Gnomad4 ASJ

AF:

0.690

Gnomad4 EAS

AF:

0.906

Gnomad4 SAS

AF:

0.309

Gnomad4 FIN

AF:

0.668

Gnomad4 NFE

AF:

0.626

Gnomad4 OTH

AF:

0.590

Alfa

AF:

0.624

Hom.:

35471

Bravo

AF:

0.520

Asia WGS

AF:

0.547

AC:

1907

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 25, 2016	- -

Congenital bile acid synthesis defect 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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