16-30985550-C-G

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.-6-103C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 1,531,530 control chromosomes in the GnomAD database, including 287,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (23377 hom., cov: 33)
  • Exomes 𝑓: 0.61 (264013 hom.)
• Consequence: HSD3B7 NM_025193.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.785

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=-0.8).
• BP6: Variant 16-30985550-C-G is Benign according to our data. Variant chr16-30985550-C-G is described in ClinVar as [Benign]. Clinvar id is 1225980.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.-6-103C>G		intron_variant		ENST00000297679.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD3B7	ENST00000297679.10	c.-6-103C>G		intron_variant		1	NM_025193.4	P1
	ENST00000624286.1	n.2721G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 79954 AN: 151678 Hom.: 23361 Cov.: 33

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.593

GnomAD3 exomes AF: 0.576 AC: 80893 AN: 140418 Hom.: 25228 AF XY: 0.564 AC XY: 42516 AN XY: 75362

Gnomad AFR exome AF: 0.249

Gnomad AMR exome AF: 0.564

Gnomad ASJ exome AF: 0.677

Gnomad EAS exome AF: 0.909

Gnomad SAS exome AF: 0.331

Gnomad FIN exome AF: 0.648

Gnomad NFE exome AF: 0.634

Gnomad OTH exome AF: 0.611

GnomAD4 exome AF: 0.610 AC: 841277 AN: 1379734 Hom.: 264013 Cov.: 53 AF XY: 0.604 AC XY: 411104 AN XY: 680688

Gnomad4 AFR exome AF: 0.260

Gnomad4 AMR exome AF: 0.567

Gnomad4 ASJ exome AF: 0.674

Gnomad4 EAS exome AF: 0.909

Gnomad4 SAS exome AF: 0.334

Gnomad4 FIN exome AF: 0.649

Gnomad4 NFE exome AF: 0.628

Gnomad4 OTH exome AF: 0.609

GnomAD4 genome AF: 0.527 AC: 80015 AN: 151796 Hom.: 23377 Cov.: 33 AF XY: 0.528 AC XY: 39136 AN XY: 74158

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.590

Alfa AF: 0.520 Hom.: 2758

Bravo AF: 0.519

Asia WGS AF: 0.546 AC: 1902 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	-0.80
Cadd	Benign	3.1
Dann	Benign	0.63

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: rs12443808; hg19: chr16-30996871; COSMIC: COSV52681234; COSMIC: COSV52681234;