rs2236780

chr1-119507840-A-Gchr1-119507840-A-T

Variant summary

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

The NM_000862.3(HSD3B1):c.145+219A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 460,690 control chromosomes in the GnomAD database, including 118,336 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 0.69 (36259 hom., cov: 32)
  • Exomes 𝑓: 0.72 (82077 hom.)
• Consequence: HSD3B1 NM_000862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.467

Genes affected

HSD3B1 (HGNC:5217): (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1) The protein encoded by this gene is an enzyme that catalyzes the oxidative conversion of delta-5-3-beta-hydroxysteroid precursors into delta-4-ketosteroids, which leads to the production of all classes of steroid hormones. The encoded protein also catalyzes the interconversion of 3-beta-hydroxy- and 3-keto-5-alpha-androstane steroids. [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD3B1	NM_000862.3	c.145+219A>G		intron_variant		ENST00000369413.8
HSD3B1	NM_001328615.1	c.145+219A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD3B1	ENST00000369413.8	c.145+219A>G		intron_variant		1	NM_000862.3	P1

Frequencies

GnomAD3 genomes AF: 0.687 AC: 104377 AN: 151970 Hom.: 36246 Cov.: 32

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.680

GnomAD4 exome AF: 0.725 AC: 223732 AN: 308602 Hom.: 82077 Cov.: 4 AF XY: 0.729 AC XY: 118457 AN XY: 162586

Gnomad4 AFR exome AF: 0.588

Gnomad4 AMR exome AF: 0.774

Gnomad4 ASJ exome AF: 0.687

Gnomad4 EAS exome AF: 0.916

Gnomad4 SAS exome AF: 0.792

Gnomad4 FIN exome AF: 0.749

Gnomad4 NFE exome AF: 0.698

Gnomad4 OTH exome AF: 0.712

GnomAD4 genome AF: 0.687 AC: 104429 AN: 152088 Hom.: 36259 Cov.: 32 AF XY: 0.695 AC XY: 51704 AN XY: 74358

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.882

Gnomad4 SAS AF: 0.807

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.684

Alfa AF: 0.686 Hom.: 5755

Bravo AF: 0.680

Asia WGS AF: 0.788 AC: 2738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.8
Dann	Benign	0.50

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: rs2236780; hg19: chr1-120050463;