rs17849880

chr16-30987877-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_025193.4(HSD3B7):c.804C>T(p.Tyr268=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.094 in 1,613,850 control chromosomes in the GnomAD database, including 8,129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (480 hom., cov: 34)
  • Exomes 𝑓: 0.097 (7649 hom.)
• Consequence: HSD3B7 NM_025193.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0240

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 16-30987877-C-T is Benign according to our data. Variant chr16-30987877-C-T is described in ClinVar as [Benign]. Clinvar id is 261874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.024 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD3B7	NM_025193.4	c.804C>T	p.Tyr268=	synonymous_variant	7/7	ENST00000297679.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD3B7	ENST00000297679.10	c.804C>T	p.Tyr268=	synonymous_variant	7/7	1	NM_025193.4	P1
	ENST00000624286.1	n.394G>A		non_coding_transcript_exon_variant	1/1
HSD3B7	ENST00000262520.10	c.*50C>T		3_prime_UTR_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.0682 AC: 10388 AN: 152206 Hom.: 480 Cov.: 34

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0518

Gnomad ASJ AF: 0.0680

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.0691

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0636

GnomAD3 exomes AF: 0.0696 AC: 17471 AN: 251178 Hom.: 803 AF XY: 0.0707 AC XY: 9601 AN XY: 135860

Gnomad AFR exome AF: 0.0173

Gnomad AMR exome AF: 0.0380

Gnomad ASJ exome AF: 0.0746

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0358

Gnomad FIN exome AF: 0.0696

Gnomad NFE exome AF: 0.106

Gnomad OTH exome AF: 0.0799

GnomAD4 exome AF: 0.0967 AC: 141269 AN: 1461526 Hom.: 7649 Cov.: 65 AF XY: 0.0944 AC XY: 68633 AN XY: 727122

Gnomad4 AFR exome AF: 0.0162

Gnomad4 AMR exome AF: 0.0404

Gnomad4 ASJ exome AF: 0.0728

Gnomad4 EAS exome AF: 0.000353

Gnomad4 SAS exome AF: 0.0369

Gnomad4 FIN exome AF: 0.0693

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.0847

GnomAD4 genome AF: 0.0682 AC: 10383 AN: 152324 Hom.: 480 Cov.: 34 AF XY: 0.0654 AC XY: 4872 AN XY: 74490

Gnomad4 AFR AF: 0.0186

Gnomad4 AMR AF: 0.0517

Gnomad4 ASJ AF: 0.0680

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0360

Gnomad4 FIN AF: 0.0691

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.0909 Hom.: 411

Bravo AF: 0.0652

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

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 10, 2016	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	8.1
Dann	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17849880; hg19: chr16-30999198; COSMIC: COSV52681027; COSMIC: COSV52681027;