rs2854964

Variant names:

• chr1-119418756-T-A
• rs2854964
• NM_000198.4:c.143-662T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-119418756-T-A
• chr1-119418756-T-C
• chr1-119418756-T-G

Variant summary

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

The NM_000198.4(HSD3B2):​c.143-662T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 151,430 control chromosomes in the GnomAD database, including 36,767 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 0.70 (36767 hom., cov: 28)
• Consequence: HSD3B2 NM_000198.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 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.143-662T>A		intron	N/A	NP_000189.1	P26439-1
	HSD3B2	NM_001166120.2		c.143-662T>A		intron	N/A	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.143-662T>A		intron	N/A	ENSP00000358424.3	P26439-1
	HSD3B2	ENST00000543831.5	TSL:3	c.143-662T>A		intron	N/A	ENSP00000445122.1	P26439-1
	HSD3B2	ENST00000902254.1		c.143-662T>A		intron	N/A	ENSP00000572313.1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105287 AN: 151326 Hom.: 36743 Cov.: 28

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.696 AC: 105356 AN: 151430 Hom.: 36767 Cov.: 28 AF XY: 0.698 AC XY: 51605 AN XY: 73940

African (AFR) AF: 0.745 AC: 30688 AN: 41198

American (AMR) AF: 0.729 AC: 11091 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2160 AN: 3462

East Asian (EAS) AF: 0.697 AC: 3585 AN: 5142

South Asian (SAS) AF: 0.639 AC: 3052 AN: 4776

European-Finnish (FIN) AF: 0.704 AC: 7359 AN: 10448

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.663 AC: 45036 AN: 67894

Other (OTH) AF: 0.676 AC: 1420 AN: 2102

Alfa AF: 0.684 Hom.: 4196

Bravo AF: 0.702

Asia WGS AF: 0.663 AC: 2311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.78
DANN	Benign	0.40
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2854964; hg19: chr1-119961379; COSMIC: COSV65592867;