1-119420831-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000198.4(HSD3B2):c.308-978T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,028 control chromosomes in the GnomAD database, including 7,029 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (7029 hom., cov: 31)
• Consequence: HSD3B2 NM_000198.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD3B2	NM_000198.4	c.308-978T>C		intron_variant		ENST00000369416.4
HSD3B2	NM_001166120.2	c.308-978T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD3B2	ENST00000369416.4	c.308-978T>C		intron_variant		1	NM_000198.4	P1
HSD3B2	ENST00000433745.5	c.308-978T>C		intron_variant		3
HSD3B2	ENST00000543831.5	c.308-978T>C		intron_variant		3		P1
HSD3B2	ENST00000448448.2	n.252-978T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37469 AN: 151908 Hom.: 7008 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.237

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.247 AC: 37538 AN: 152028 Hom.: 7029 Cov.: 31 AF XY: 0.247 AC XY: 18388 AN XY: 74338

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.0886

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.237

Alfa AF: 0.136 Hom.: 815

Bravo AF: 0.268

Asia WGS AF: 0.268 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	7.1
Dann	Benign	0.76

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: rs3765948; hg19: chr1-119963454;