1-119507840-A-T

Variant names:

• chr1-119507840-A-T
• rs2236780
• NM_000862.3:c.145+219A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000862.3(HSD3B1):​c.145+219A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSD3B1 NM_000862.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.467
• Publications: 9 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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.145+219A>T		intron	N/A	NP_000853.1	P14060
	HSD3B1	NM_001328615.1		c.145+219A>T		intron	N/A	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.145+219A>T		intron	N/A	ENSP00000358421.3	P14060
	HSD3B1	ENST00000528909.1	TSL:1	c.145+219A>T		intron	N/A	ENSP00000432268.1	P14060
	HSD3B1	ENST00000531340.5	TSL:3	c.145+219A>T		intron	N/A	ENSP00000435999.1	E9PRN7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 309482 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 163054

African (AFR) AF: 0.00 AC: 0 AN: 9128

American (AMR) AF: 0.00 AC: 0 AN: 13176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9408

East Asian (EAS) AF: 0.00 AC: 0 AN: 19418

South Asian (SAS) AF: 0.00 AC: 0 AN: 32710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1320

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 189604

Other (OTH) AF: 0.00 AC: 0 AN: 17740

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 5755

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.41
PhyloP100		0.47

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: rs2236780; hg19: chr1-120050463;