rs4659175

Variant names:

• chr1-119413850-T-C
• rs4659175
• ENST00000902254.1:c.-1570T>C

Variant summary

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

The ENST00000902254.1(HSD3B2):​c.-1570T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,004 control chromosomes in the GnomAD database, including 37,208 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 (37208 hom., cov: 32)
• Consequence: HSD3B2 ENST00000902254.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607
• Publications: 9 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)

ENSG00000307032 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000902254.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD3B2	ENST00000902254.1		c.-1570T>C		5_prime_UTR	Exon 1 of 3	ENSP00000572313.1
	ENSG00000307032	ENST00000823009.1		n.504-447A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106145 AN: 151886 Hom.: 37179 Cov.: 32

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.699 AC: 106227 AN: 152004 Hom.: 37208 Cov.: 32 AF XY: 0.701 AC XY: 52113 AN XY: 74306

African (AFR) AF: 0.749 AC: 31056 AN: 41490

American (AMR) AF: 0.728 AC: 11121 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2197 AN: 3468

East Asian (EAS) AF: 0.698 AC: 3601 AN: 5158

South Asian (SAS) AF: 0.648 AC: 3120 AN: 4816

European-Finnish (FIN) AF: 0.706 AC: 7443 AN: 10546

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45291 AN: 67932

Other (OTH) AF: 0.676 AC: 1430 AN: 2114

Alfa AF: 0.675 Hom.: 51701

Bravo AF: 0.704

Asia WGS AF: 0.665 AC: 2312 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.13
DANN	Benign	0.53
PhyloP100		-0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4659175;

hg19: chr1-119956473;