1-119508823-G-A

Variant names:

• chr1-119508823-G-A
• rs3765945
• NM_000862.3:c.145+1202G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000862.3(HSD3B1):​c.145+1202G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,052 control chromosomes in the GnomAD database, including 28,446 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 0.59 (28446 hom., cov: 32)
• Consequence: HSD3B1 NM_000862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 14 publications found

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]

ENSG00000293080 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000862.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD3B1	NM_000862.3	MANE Select	c.145+1202G>A		intron	N/A	NP_000853.1
	HSD3B1	NM_001328615.1		c.145+1202G>A		intron	N/A	NP_001315544.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD3B1	ENST00000369413.8	TSL:1 MANE Select	c.145+1202G>A		intron	N/A	ENSP00000358421.3
	HSD3B1	ENST00000528909.1	TSL:1	c.145+1202G>A		intron	N/A	ENSP00000432268.1
	HSD3B1	ENST00000531340.5	TSL:3	c.145+1202G>A		intron	N/A	ENSP00000435999.1

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89850 AN: 151934 Hom.: 28441 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.591 AC: 89874 AN: 152052 Hom.: 28446 Cov.: 32 AF XY: 0.603 AC XY: 44833 AN XY: 74310

African (AFR) AF: 0.354 AC: 14678 AN: 41460

American (AMR) AF: 0.703 AC: 10740 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2265 AN: 3472

East Asian (EAS) AF: 0.878 AC: 4541 AN: 5170

South Asian (SAS) AF: 0.767 AC: 3693 AN: 4816

European-Finnish (FIN) AF: 0.736 AC: 7765 AN: 10550

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 44006 AN: 67978

Other (OTH) AF: 0.603 AC: 1276 AN: 2116

Alfa AF: 0.632 Hom.: 132229

Bravo AF: 0.577

Asia WGS AF: 0.761 AC: 2647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.025
DANN	Benign	0.27
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3765945; hg19: chr1-120051446; COSMIC: COSV52489917; COSMIC: COSV52489917;