rs1047303

Variant names:

• chr1-119514623-C-A
• rs1047303
• NM_000862.3:c.1100C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-119514623-C-A
• chr1-119514623-C-G
• chr1-119514623-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_000862.3(HSD3B1):​c.1100C>A​(p.Thr367Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 1,613,074 control chromosomes in the GnomAD database, including 412,097 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,drug response (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44941 hom., cov: 29)
  • Exomes 𝑓: 0.71 (367156 hom.)
• Consequence: HSD3B1 NM_000862.3 missense
• Clinical Significance: Benign; drug response criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: -0.311
• Publications: 94 publications found

Genes affected

HSD3B1 (HGNC:5217): (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1) The protein encoded by this gene is an enzyme that catalyzes the oxidative conversion of delta-5-3-beta-hydroxysteroid precursors into delta-4-ketosteroids, which leads to the production of all classes of steroid hormones. The encoded protein also catalyzes the interconversion of 3-beta-hydroxy- and 3-keto-5-alpha-androstane steroids. [provided by RefSeq, Jun 2016]

ENSG00000293080 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.1095348E-6).
• BP6: Variant 1-119514623-C-A is Benign according to our data. Variant chr1-119514623-C-A is described in ClinVar as Benign|drug_response. ClinVar VariationId is 1274004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000862.3. 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
	HSD3B1	NM_000862.3	MANE Select	c.1100C>A	p.Thr367Asn	missense	Exon 4 of 4	NP_000853.1	P14060
	HSD3B1	NM_001328615.1		c.1100C>A	p.Thr367Asn	missense	Exon 4 of 4	NP_001315544.1	P14060

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD3B1	ENST00000369413.8	TSL:1 MANE Select	c.1100C>A	p.Thr367Asn	missense	Exon 4 of 4	ENSP00000358421.3	P14060
	HSD3B1	ENST00000528909.1	TSL:1	c.1100C>A	p.Thr367Asn	missense	Exon 3 of 3	ENSP00000432268.1	P14060
	ENSG00000293080	ENST00000632456.2	TSL:6	n.243-24511G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.764 AC: 115773 AN: 151570 Hom.: 44897 Cov.: 29

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.727

GnomAD2 exomes AF: 0.755 AC: 188429 AN: 249654 AF XY: 0.748

Gnomad AFR exome AF: 0.892

Gnomad AMR exome AF: 0.850

Gnomad ASJ exome AF: 0.666

Gnomad EAS exome AF: 0.937

Gnomad FIN exome AF: 0.741

Gnomad NFE exome AF: 0.674

Gnomad OTH exome AF: 0.718

GnomAD4 exome AF: 0.705 AC: 1030890 AN: 1461386 Hom.: 367156 Cov.: 61 AF XY: 0.707 AC XY: 513679 AN XY: 726994

African (AFR) AF: 0.895 AC: 29947 AN: 33472

American (AMR) AF: 0.840 AC: 37513 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 17497 AN: 26128

East Asian (EAS) AF: 0.939 AC: 37206 AN: 39638

South Asian (SAS) AF: 0.808 AC: 69644 AN: 86242

European-Finnish (FIN) AF: 0.742 AC: 39651 AN: 53410

Middle Eastern (MID) AF: 0.646 AC: 3721 AN: 5756

European-Non Finnish (NFE) AF: 0.677 AC: 752348 AN: 1111690

Other (OTH) AF: 0.718 AC: 43363 AN: 60376

GnomAD4 genome AF: 0.764 AC: 115875 AN: 151688 Hom.: 44941 Cov.: 29 AF XY: 0.771 AC XY: 57102 AN XY: 74092

African (AFR) AF: 0.884 AC: 36589 AN: 41384

American (AMR) AF: 0.789 AC: 12014 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2325 AN: 3468

East Asian (EAS) AF: 0.924 AC: 4748 AN: 5140

South Asian (SAS) AF: 0.825 AC: 3959 AN: 4798

European-Finnish (FIN) AF: 0.746 AC: 7806 AN: 10470

Middle Eastern (MID) AF: 0.675 AC: 197 AN: 292

European-Non Finnish (NFE) AF: 0.677 AC: 45963 AN: 67898

Other (OTH) AF: 0.731 AC: 1534 AN: 2098

Alfa AF: 0.711 Hom.: 17051

Bravo AF: 0.771

TwinsUK AF: 0.675 AC: 2504

ALSPAC AF: 0.671 AC: 2585

ESP6500AA AF: 0.881 AC: 3879

ESP6500EA AF: 0.682 AC: 5860

ExAC AF: 0.755 AC: 91615

Asia WGS AF: 0.866 AC: 3011 AN: 3478

EpiCase AF: 0.657

EpiControl AF: 0.659

ClinVar

ClinVar submissions

Significance: Benign; drug response

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	-	Androgen deprivation therapy response (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.078
DANN	Benign	0.26
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		-0.31
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.13
Sift	Benign	0.30	T
Sift4G	Benign	0.30	T
Polyphen		0.021	B
Vest4		0.093
MPC		0.029
ClinPred		0.0099	T
GERP RS		-0.043
Varity_R		0.046
gMVP		0.42
Mutation Taster		=98/2	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: rs1047303; hg19: chr1-120057246; COSMIC: COSV52489946; COSMIC: COSV52489946;