1-119422941-C-G

Position:

• chr1-119422941-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000198.4(HSD3B2):​c.*321C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 470,306 control chromosomes in the GnomAD database, including 8,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3645 hom., cov: 32)
  • Exomes 𝑓: 0.15 (4788 hom.)
• Consequence: HSD3B2 NM_000198.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.632

Genes affected

HSD3B2 (HGNC:5218): (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2) The protein encoded by this gene is a bifunctional enzyme that catalyzes the oxidative conversion of delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. It plays a crucial role in the biosynthesis of all classes of hormonal steroids. This gene is predominantly expressed in the adrenals and the gonads. Mutations in this gene are associated with 3-beta-hydroxysteroid dehydrogenase, type II, deficiency. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-119422941-C-G is Benign according to our data. Variant chr1-119422941-C-G is described in ClinVar as [Benign]. Clinvar id is 292275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD3B2	NM_000198.4	c.*321C>G		3_prime_UTR_variant	4/4	ENST00000369416.4	NP_000189.1
HSD3B2	NM_001166120.2	c.*321C>G		3_prime_UTR_variant	4/4		NP_001159592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD3B2	ENST00000369416.4	c.*321C>G		3_prime_UTR_variant	4/4	1	NM_000198.4	ENSP00000358424.3
HSD3B2	ENST00000543831.5	c.*321C>G		3_prime_UTR_variant	4/4	3		ENSP00000445122.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29198 AN: 152170 Hom.: 3633 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.0871

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.197

GnomAD4 exome AF: 0.153 AC: 48613 AN: 318018 Hom.: 4788 Cov.: 0 AF XY: 0.157 AC XY: 25969 AN XY: 165156

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.176

Gnomad4 ASJ exome AF: 0.198

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.0874

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.192 AC: 29251 AN: 152288 Hom.: 3645 Cov.: 32 AF XY: 0.194 AC XY: 14476 AN XY: 74476

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.0871

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.198

Alfa AF: 0.0589 Hom.: 74

Bravo AF: 0.206

Asia WGS AF: 0.258 AC: 900 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

3 beta-Hydroxysteroid dehydrogenase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.94
DANN	Benign	0.84

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: rs1361530; hg19: chr1-119965564;