1-119420831-T-C

Variant names:

• chr1-119420831-T-C
• rs3765948
• NM_000198.4:c.308-978T>C

Variant summary

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

The NM_000198.4(HSD3B2):​c.308-978T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,028 control chromosomes in the GnomAD database, including 7,029 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 0.25 (7029 hom., cov: 31)
• Consequence: HSD3B2 NM_000198.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• Publications: 3 publications found

Genes affected

HSD3B2 (HGNC:5218): (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2) The protein encoded by this gene is a bifunctional enzyme that catalyzes the oxidative conversion of delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. It plays a crucial role in the biosynthesis of all classes of hormonal steroids. This gene is predominantly expressed in the adrenals and the gonads. Mutations in this gene are associated with 3-beta-hydroxysteroid dehydrogenase, type II, deficiency. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2009]

HSD3B2 Gene-Disease associations (from GenCC):

• congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD3B2	NM_000198.4	c.308-978T>C		intron_variant	Intron 3 of 3	ENST00000369416.4	NP_000189.1
HSD3B2	NM_001166120.2	c.308-978T>C		intron_variant	Intron 3 of 3		NP_001159592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD3B2	ENST00000369416.4	c.308-978T>C		intron_variant	Intron 3 of 3	1	NM_000198.4	ENSP00000358424.3
HSD3B2	ENST00000543831.5	c.308-978T>C		intron_variant	Intron 3 of 3	3		ENSP00000445122.1
HSD3B2	ENST00000433745.5	c.308-978T>C		intron_variant	Intron 3 of 3	3		ENSP00000388292.1
HSD3B2	ENST00000448448.2	n.252-978T>C		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37469 AN: 151908 Hom.: 7008 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.247 AC: 37538 AN: 152028 Hom.: 7029 Cov.: 31 AF XY: 0.247 AC XY: 18388 AN XY: 74338

African (AFR) AF: 0.522 AC: 21613 AN: 41394

American (AMR) AF: 0.211 AC: 3228 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 786 AN: 3470

East Asian (EAS) AF: 0.254 AC: 1310 AN: 5166

South Asian (SAS) AF: 0.257 AC: 1239 AN: 4818

European-Finnish (FIN) AF: 0.0886 AC: 940 AN: 10610

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7644 AN: 67984

Other (OTH) AF: 0.237 AC: 499 AN: 2104

Alfa AF: 0.147 Hom.: 1090

Bravo AF: 0.268

Asia WGS AF: 0.268 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.1
DANN	Benign	0.76
PhyloP100		0.26
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: rs3765948; hg19: chr1-119963454;