1-119512152-A-G

Variant names:

• chr1-119512152-A-G
• rs6428830
• NM_000862.3:c.310+485A>G

Variant summary

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

The NM_000862.3(HSD3B1):​c.310+485A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,128 control chromosomes in the GnomAD database, including 46,852 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 0.78 (46852 hom., cov: 32)
• Consequence: HSD3B1 NM_000862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD3B1	NM_000862.3	c.310+485A>G		intron_variant	Intron 3 of 3	ENST00000369413.8	NP_000853.1
HSD3B1	NM_001328615.1	c.310+485A>G		intron_variant	Intron 3 of 3		NP_001315544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD3B1	ENST00000369413.8	c.310+485A>G		intron_variant	Intron 3 of 3	1	NM_000862.3	ENSP00000358421.3
HSD3B1	ENST00000528909.1	c.310+485A>G		intron_variant	Intron 2 of 2	1		ENSP00000432268.1
HSD3B1	ENST00000492140.1	n.*200A>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118571 AN: 152010 Hom.: 46805 Cov.: 32

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.780 AC: 118675 AN: 152128 Hom.: 46852 Cov.: 32 AF XY: 0.786 AC XY: 58481 AN XY: 74366

Gnomad4 AFR AF: 0.888

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.923

Gnomad4 SAS AF: 0.862

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.756

Alfa AF: 0.734 Hom.: 19987

Bravo AF: 0.787

Asia WGS AF: 0.877 AC: 3049 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.9
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6428830; hg19: chr1-120054775;