16-30985474-C-T

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.-7+177C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0955 in 1,486,078 control chromosomes in the GnomAD database, including 7,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.068 (479 hom., cov: 33)
  • Exomes 𝑓: 0.099 (7188 hom.)
• Consequence: HSD3B7 NM_025193.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.15

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=-0.91).
• BP6: Variant 16-30985474-C-T is Benign according to our data. Variant chr16-30985474-C-T is described in ClinVar as [Benign]. Clinvar id is 1281644.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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.-7+177C>T		intron_variant		ENST00000297679.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD3B7	ENST00000297679.10	c.-7+177C>T		intron_variant		1	NM_025193.4	P1
	ENST00000624286.1	n.2797G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0684 AC: 10417 AN: 152184 Hom.: 479 Cov.: 33

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0519

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0362

Gnomad FIN AF: 0.0689

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0636

GnomAD3 exomes AF: 0.0636 AC: 6559 AN: 103194 Hom.: 290 AF XY: 0.0651 AC XY: 3502 AN XY: 53824

Gnomad AFR exome AF: 0.0168

Gnomad AMR exome AF: 0.0374

Gnomad ASJ exome AF: 0.0768

Gnomad EAS exome AF: 0.000391

Gnomad SAS exome AF: 0.0346

Gnomad FIN exome AF: 0.0638

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.0731

GnomAD4 exome AF: 0.0986 AC: 131478 AN: 1333776 Hom.: 7188 Cov.: 31 AF XY: 0.0964 AC XY: 62865 AN XY: 652024

Gnomad4 AFR exome AF: 0.0164

Gnomad4 AMR exome AF: 0.0401

Gnomad4 ASJ exome AF: 0.0719

Gnomad4 EAS exome AF: 0.000313

Gnomad4 SAS exome AF: 0.0371

Gnomad4 FIN exome AF: 0.0688

Gnomad4 NFE exome AF: 0.112

Gnomad4 OTH exome AF: 0.0851

GnomAD4 genome AF: 0.0684 AC: 10412 AN: 152302 Hom.: 479 Cov.: 33 AF XY: 0.0655 AC XY: 4879 AN XY: 74476

Gnomad4 AFR AF: 0.0192

Gnomad4 AMR AF: 0.0518

Gnomad4 ASJ AF: 0.0677

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0361

Gnomad4 FIN AF: 0.0689

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.0630

Alfa AF: 0.0819 Hom.: 157

Bravo AF: 0.0654

Asia WGS AF: 0.0160 AC: 56 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.68
Dann	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs79974799; hg19: chr16-30996795;