chr1-119508823-G-A

Position:

• chr1-119508823-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

HSD3B1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD3B1	NM_000862.3	c.145+1202G>A		intron_variant		ENST00000369413.8	NP_000853.1
HSD3B1	NM_001328615.1	c.145+1202G>A		intron_variant			NP_001315544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD3B1	ENST00000369413.8	c.145+1202G>A		intron_variant		1	NM_000862.3	ENSP00000358421.3
HSD3B1	ENST00000528909.1	c.145+1202G>A		intron_variant		1		ENSP00000432268.1
HSD3B1	ENST00000531340.5	c.145+1202G>A		intron_variant		3		ENSP00000435999.1
HSD3B1	ENST00000492140.1	n.280+1202G>A		intron_variant		2

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

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.878

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.603

Alfa AF: 0.642 Hom.: 63797

Bravo AF: 0.577

Asia WGS AF: 0.761 AC: 2647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.025
DANN	Benign	0.27

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