rs1843090

Positions:

• chr15-74350693-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000781.3(CYP11A1):​c.270-2638T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 152,084 control chromosomes in the GnomAD database, including 32,523 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 0.65 (32501 hom., cov: 31)
  • Exomes 𝑓: 0.67 (22 hom.)
• Consequence: CYP11A1 NM_000781.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85

Genes affected

CYP11A1 (HGNC:2590): (cytochrome P450 family 11 subfamily A member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the mitochondrial inner membrane and catalyzes the conversion of cholesterol to pregnenolone, the first and rate-limiting step in the synthesis of the steroid hormones. Two transcript variants encoding different isoforms have been found for this gene. The cellular location of the smaller isoform is unclear since it lacks the mitochondrial-targeting transit peptide. [provided by RefSeq, Jul 2008]

CYP11A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP11A1	NM_000781.3	c.270-2638T>C		intron_variant		ENST00000268053.11	NP_000772.2
CYP11A1	NM_001099773.2	c.-205-2638T>C		intron_variant			NP_001093243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP11A1	ENST00000268053.11	c.270-2638T>C		intron_variant		1	NM_000781.3	ENSP00000268053.6

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98754 AN: 151868 Hom.: 32491 Cov.: 31

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.633

GnomAD4 exome AF: 0.667 AC: 64 AN: 96 Hom.: 22 AF XY: 0.667 AC XY: 44 AN XY: 66

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.875

Gnomad4 NFE exome AF: 0.679

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.650 AC: 98801 AN: 151988 Hom.: 32501 Cov.: 31 AF XY: 0.649 AC XY: 48232 AN XY: 74296

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.762

Gnomad4 NFE AF: 0.710

Gnomad4 OTH AF: 0.626

Alfa AF: 0.688 Hom.: 51372

Bravo AF: 0.641

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs1843090; hg19: chr15-74643034;