chr1-119513321-A-T

Position:

• chr1-119513321-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.311-513A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0527 in 152,212 control chromosomes in the GnomAD database, including 588 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 0.053 (588 hom., cov: 32)
• Consequence: HSD3B1 NM_000862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD3B1	NM_000862.3	c.311-513A>T		intron_variant		ENST00000369413.8	NP_000853.1
HSD3B1	NM_001328615.1	c.311-513A>T		intron_variant			NP_001315544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD3B1	ENST00000369413.8	c.311-513A>T		intron_variant		1	NM_000862.3	ENSP00000358421	P1
HSD3B1	ENST00000528909.1	c.311-513A>T		intron_variant		1		ENSP00000432268	P1

Frequencies

GnomAD3 genomes AF: 0.0525 AC: 7986 AN: 152094 Hom.: 585 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0381

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.0419

Gnomad SAS AF: 0.0408

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00144

Gnomad OTH AF: 0.0407

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

GnomAD4 genome AF: 0.0527 AC: 8020 AN: 152212 Hom.: 588 Cov.: 32 AF XY: 0.0522 AC XY: 3884 AN XY: 74436

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.0382

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.0420

Gnomad4 SAS AF: 0.0415

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.00144

Gnomad4 OTH AF: 0.0412

Alfa AF: 0.0421 Hom.: 53

Bravo AF: 0.0619

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.051
DANN	Benign	0.55

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: rs3765944; hg19: chr1-120055944;