rs1361530

Variant names:

• chr1-119422941-C-G
• rs1361530
• NM_000198.4:c.*321C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-119422941-C-G
• chr1-119422941-C-A
• chr1-119422941-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000198.4(HSD3B2):​c.*321C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 470,306 control chromosomes in the GnomAD database, including 8,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3645 hom., cov: 32)
  • Exomes 𝑓: 0.15 (4788 hom.)
• Consequence: HSD3B2 NM_000198.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.632
• Publications: 5 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: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-119422941-C-G is Benign according to our data. Variant chr1-119422941-C-G is described in ClinVar as Benign. ClinVar VariationId is 292275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000198.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD3B2	NM_000198.4	MANE Select	c.*321C>G		3_prime_UTR	Exon 4 of 4	NP_000189.1	P26439-1
	HSD3B2	NM_001166120.2		c.*321C>G		3_prime_UTR	Exon 4 of 4	NP_001159592.1	P26439-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD3B2	ENST00000369416.4	TSL:1 MANE Select	c.*321C>G		3_prime_UTR	Exon 4 of 4	ENSP00000358424.3	P26439-1
	HSD3B2	ENST00000543831.5	TSL:3	c.*321C>G		3_prime_UTR	Exon 4 of 4	ENSP00000445122.1	P26439-1
	HSD3B2	ENST00000902254.1		c.*321C>G		3_prime_UTR	Exon 3 of 3	ENSP00000572313.1

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29198 AN: 152170 Hom.: 3633 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.0871

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.197

GnomAD4 exome AF: 0.153 AC: 48613 AN: 318018 Hom.: 4788 Cov.: 0 AF XY: 0.157 AC XY: 25969 AN XY: 165156

African (AFR) AF: 0.339 AC: 3487 AN: 10292

American (AMR) AF: 0.176 AC: 2062 AN: 11710

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 2132 AN: 10768

East Asian (EAS) AF: 0.322 AC: 7050 AN: 21886

South Asian (SAS) AF: 0.243 AC: 8557 AN: 35164

European-Finnish (FIN) AF: 0.0874 AC: 1334 AN: 15258

Middle Eastern (MID) AF: 0.223 AC: 316 AN: 1414

European-Non Finnish (NFE) AF: 0.108 AC: 20848 AN: 192506

Other (OTH) AF: 0.149 AC: 2827 AN: 19020

GnomAD4 genome AF: 0.192 AC: 29251 AN: 152288 Hom.: 3645 Cov.: 32 AF XY: 0.194 AC XY: 14476 AN XY: 74476

African (AFR) AF: 0.341 AC: 14175 AN: 41538

American (AMR) AF: 0.189 AC: 2891 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 749 AN: 3468

East Asian (EAS) AF: 0.252 AC: 1305 AN: 5180

South Asian (SAS) AF: 0.254 AC: 1227 AN: 4830

European-Finnish (FIN) AF: 0.0871 AC: 925 AN: 10614

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7292 AN: 68028

Other (OTH) AF: 0.198 AC: 418 AN: 2114

Alfa AF: 0.0589 Hom.: 74

Bravo AF: 0.206

Asia WGS AF: 0.258 AC: 900 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	3 beta-Hydroxysteroid dehydrogenase deficiency (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.94
DANN	Benign	0.84
PhyloP100		-0.63
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: rs1361530; hg19: chr1-119965564;