1-119514535-C-T

Variant names:

• chr1-119514535-C-T
• rs6203
• NM_000862.3:c.1012C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000862.3(HSD3B1):​c.1012C>T​(p.Leu338Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,613,554 control chromosomes in the GnomAD database, including 159,076 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 0.36 (12170 hom., cov: 30)
  • Exomes 𝑓: 0.44 (146906 hom.)
• Consequence: HSD3B1 NM_000862.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 42 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=1.25 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 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.1012C>T	p.Leu338Leu	synonymous	Exon 4 of 4	NP_000853.1	P14060
	HSD3B1	NM_001328615.1		c.1012C>T	p.Leu338Leu	synonymous	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.1012C>T	p.Leu338Leu	synonymous	Exon 4 of 4	ENSP00000358421.3	P14060
	HSD3B1	ENST00000528909.1	TSL:1	c.1012C>T	p.Leu338Leu	synonymous	Exon 3 of 3	ENSP00000432268.1	P14060
	ENSG00000293080	ENST00000632456.2	TSL:6	n.243-24423G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54643 AN: 151654 Hom.: 12174 Cov.: 30

Gnomad AFR AF: 0.0946

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.365

GnomAD2 exomes AF: 0.451 AC: 113324 AN: 251016 AF XY: 0.451

Gnomad AFR exome AF: 0.0811

Gnomad AMR exome AF: 0.569

Gnomad ASJ exome AF: 0.356

Gnomad EAS exome AF: 0.672

Gnomad FIN exome AF: 0.539

Gnomad NFE exome AF: 0.436

Gnomad OTH exome AF: 0.447

GnomAD4 exome AF: 0.441 AC: 644912 AN: 1461782 Hom.: 146906 Cov.: 66 AF XY: 0.440 AC XY: 320134 AN XY: 727200

African (AFR) AF: 0.0739 AC: 2474 AN: 33478

American (AMR) AF: 0.555 AC: 24810 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 9394 AN: 26136

East Asian (EAS) AF: 0.663 AC: 26322 AN: 39682

South Asian (SAS) AF: 0.410 AC: 35381 AN: 86256

European-Finnish (FIN) AF: 0.537 AC: 28708 AN: 53416

Middle Eastern (MID) AF: 0.322 AC: 1857 AN: 5768

European-Non Finnish (NFE) AF: 0.441 AC: 489882 AN: 1111940

Other (OTH) AF: 0.432 AC: 26084 AN: 60394

GnomAD4 genome AF: 0.360 AC: 54644 AN: 151772 Hom.: 12170 Cov.: 30 AF XY: 0.372 AC XY: 27559 AN XY: 74148

African (AFR) AF: 0.0943 AC: 3908 AN: 41444

American (AMR) AF: 0.475 AC: 7226 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1193 AN: 3462

East Asian (EAS) AF: 0.656 AC: 3362 AN: 5122

South Asian (SAS) AF: 0.415 AC: 1991 AN: 4802

European-Finnish (FIN) AF: 0.556 AC: 5843 AN: 10504

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.437 AC: 29647 AN: 67918

Other (OTH) AF: 0.366 AC: 768 AN: 2100

Alfa AF: 0.406 Hom.: 4269

Bravo AF: 0.346

Asia WGS AF: 0.473 AC: 1646 AN: 3478

EpiCase AF: 0.423

EpiControl AF: 0.423

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.2
DANN	Benign	0.60
PhyloP100		1.3
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: rs6203; hg19: chr1-120057158; COSMIC: COSV52489861; COSMIC: COSV52489861;