rs149918713

chr16-30988048-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.05

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]

(HGNC:):

ACMG classification

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. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD3B7	NM_025193.4	c.975C>T	p.Ala325=	synonymous_variant	7/7	ENST00000297679.10

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00939 AC: 1429 AN: 152238 Hom.: 13 Cov.: 34

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.: 16 AF XY: 0.00903 AC XY: 1201 AN XY: 132990

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.: 64 AF XY: 0.0130 AC XY: 9429 AN XY: 723942

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.: 13 Cov.: 34 AF XY: 0.00961 AC XY: 716 AN XY: 74508

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.: 7

Bravo AF: 0.00866

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 19, 2024

- -

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

Other links and lift over

dbSNP: rs149918713; hg19: chr16-30999369;