rs1819698

Variant names:

• chr1-119422896-C-T
• rs1819698
• NM_000198.4:c.*276C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-119422896-C-T
• chr1-119422896-C-G

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.*276C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 542,030 control chromosomes in the GnomAD database, including 13,753 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (6746 hom., cov: 32)
  • Exomes 𝑓: 0.16 (7007 hom.)
• Consequence: HSD3B2 NM_000198.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.682
• Publications: 13 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=-1.02).
• BP6: Variant 1-119422896-C-T is Benign according to our data. Variant chr1-119422896-C-T is described in ClinVar as Benign. ClinVar VariationId is 292274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 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.*276C>T		3_prime_UTR	Exon 4 of 4	NP_000189.1	P26439-1
	HSD3B2	NM_001166120.2		c.*276C>T		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.*276C>T		3_prime_UTR	Exon 4 of 4	ENSP00000358424.3	P26439-1
	HSD3B2	ENST00000543831.5	TSL:3	c.*276C>T		3_prime_UTR	Exon 4 of 4	ENSP00000445122.1	P26439-1
	HSD3B2	ENST00000902254.1		c.*276C>T		3_prime_UTR	Exon 3 of 3	ENSP00000572313.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36940 AN: 152002 Hom.: 6732 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.0886

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.164 AC: 64105 AN: 389914 Hom.: 7007 Cov.: 2 AF XY: 0.167 AC XY: 34378 AN XY: 205274

African (AFR) AF: 0.504 AC: 5770 AN: 11446

American (AMR) AF: 0.195 AC: 3120 AN: 16002

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 2604 AN: 12284

East Asian (EAS) AF: 0.327 AC: 8714 AN: 26644

South Asian (SAS) AF: 0.252 AC: 10758 AN: 42630

European-Finnish (FIN) AF: 0.0888 AC: 1979 AN: 22296

Middle Eastern (MID) AF: 0.238 AC: 400 AN: 1678

European-Non Finnish (NFE) AF: 0.115 AC: 26893 AN: 234206

Other (OTH) AF: 0.170 AC: 3867 AN: 22728

GnomAD4 genome AF: 0.243 AC: 36999 AN: 152116 Hom.: 6746 Cov.: 32 AF XY: 0.244 AC XY: 18118 AN XY: 74376

African (AFR) AF: 0.510 AC: 21107 AN: 41408

American (AMR) AF: 0.210 AC: 3207 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3466

East Asian (EAS) AF: 0.254 AC: 1313 AN: 5178

South Asian (SAS) AF: 0.256 AC: 1236 AN: 4822

European-Finnish (FIN) AF: 0.0886 AC: 940 AN: 10612

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7641 AN: 68026

Other (OTH) AF: 0.234 AC: 496 AN: 2116

Alfa AF: 0.187 Hom.: 695

Bravo AF: 0.264

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	3 beta-Hydroxysteroid dehydrogenase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.2
DANN	Benign	0.42
PhyloP100		0.68
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: rs1819698; hg19: chr1-119965519;