rs2305880
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_025193.4(HSD3B7):āc.1068T>Cā(p.Arg356=) 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 (ā ā ).
Frequency
Genomes: š 0.53 ( 23616 hom., cov: 33)
Exomes š: 0.61 ( 278464 hom. )
Consequence
HSD3B7
NM_025193.4 synonymous
NM_025193.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.85
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]
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=-0.65).
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 | UniProt |
---|---|---|---|---|---|---|---|
HSD3B7 | NM_025193.4 | c.1068T>C | p.Arg356= | synonymous_variant | 7/7 | ENST00000297679.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSD3B7 | ENST00000297679.10 | c.1068T>C | p.Arg356= | synonymous_variant | 7/7 | 1 | NM_025193.4 | P1 | |
ENST00000624286.1 | n.130A>G | non_coding_transcript_exon_variant | 1/1 | ||||||
HSD3B7 | ENST00000262520.10 | c.*314T>C | 3_prime_UTR_variant | 6/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.529 AC: 80507AN: 152070Hom.: 23600 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
80507
AN:
152070
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.587 AC: 141223AN: 240682Hom.: 44486 AF XY: 0.581 AC XY: 75975AN XY: 130876
GnomAD3 exomes
AF:
AC:
141223
AN:
240682
Hom.:
AF XY:
AC XY:
75975
AN XY:
130876
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.610 AC: 886154AN: 1452828Hom.: 278464 Cov.: 60 AF XY: 0.604 AC XY: 436546AN XY: 722678
GnomAD4 exome
AF:
AC:
886154
AN:
1452828
Hom.:
Cov.:
60
AF XY:
AC XY:
436546
AN XY:
722678
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.529 AC: 80568AN: 152188Hom.: 23616 Cov.: 33 AF XY: 0.531 AC XY: 39477AN XY: 74398
GnomAD4 genome
?
AF:
AC:
80568
AN:
152188
Hom.:
Cov.:
33
AF XY:
AC XY:
39477
AN XY:
74398
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1907
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
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 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Congenital bile acid synthesis defect 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at