16-30985551-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_025193.4(HSD3B7):c.-6-102G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 1,531,610 control chromosomes in the GnomAD database, including 304,140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (29507 hom., cov: 33)
  • Exomes 𝑓: 0.62 (274633 hom.)
• Consequence: HSD3B7 NM_025193.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.336

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 16-30985551-G-C is Benign according to our data. Variant chr16-30985551-G-C is described in ClinVar as [Benign]. Clinvar id is 1249803.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD3B7	NM_025193.4	c.-6-102G>C		intron_variant		ENST00000297679.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD3B7	ENST00000297679.10	c.-6-102G>C		intron_variant		1	NM_025193.4	P1
	ENST00000624286.1	n.2720C>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 93848 AN: 151618 Hom.: 29480 Cov.: 33

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.659

GnomAD3 exomes AF: 0.602 AC: 84592 AN: 140606 Hom.: 26957 AF XY: 0.585 AC XY: 44106 AN XY: 75448

Gnomad AFR exome AF: 0.563

Gnomad AMR exome AF: 0.586

Gnomad ASJ exome AF: 0.684

Gnomad EAS exome AF: 0.909

Gnomad SAS exome AF: 0.338

Gnomad FIN exome AF: 0.649

Gnomad NFE exome AF: 0.641

Gnomad OTH exome AF: 0.630

GnomAD4 exome AF: 0.625 AC: 861848 AN: 1379874 Hom.: 274633 Cov.: 54 AF XY: 0.618 AC XY: 420557 AN XY: 680740

Gnomad4 AFR exome AF: 0.573

Gnomad4 AMR exome AF: 0.591

Gnomad4 ASJ exome AF: 0.680

Gnomad4 EAS exome AF: 0.909

Gnomad4 SAS exome AF: 0.341

Gnomad4 FIN exome AF: 0.650

Gnomad4 NFE exome AF: 0.635

Gnomad4 OTH exome AF: 0.635

GnomAD4 genome AF: 0.619 AC: 93931 AN: 151736 Hom.: 29507 Cov.: 33 AF XY: 0.616 AC XY: 45694 AN XY: 74124

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.655

Alfa AF: 0.575 Hom.: 3264

Bravo AF: 0.623

Asia WGS AF: 0.576 AC: 2009 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	3.1
Dann	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs12443627; hg19: chr16-30996872; COSMIC: COSV52681238; COSMIC: COSV52681238;