rs1484215

Positions:

• chr15-74347768-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000781.3(CYP11A1):​c.425+132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0766 in 790,358 control chromosomes in the GnomAD database, including 3,144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.062 (402 hom., cov: 32)
  • Exomes 𝑓: 0.080 (2742 hom.)
• Consequence: CYP11A1 NM_000781.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-74347768-C-T is Benign according to our data. Variant chr15-74347768-C-T is described in ClinVar as [Benign]. Clinvar id is 1270755.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP11A1	NM_000781.3	c.425+132G>A		intron_variant		ENST00000268053.11
CYP11A1	NM_001099773.2	c.-50+132G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP11A1	ENST00000268053.11	c.425+132G>A		intron_variant		1	NM_000781.3	P1

Frequencies

GnomAD3 genomes AF: 0.0620 AC: 9433 AN: 152080 Hom.: 403 Cov.: 32

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0604

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.0521

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0689

Gnomad OTH AF: 0.0709

GnomAD4 exome AF: 0.0801 AC: 51127 AN: 638160 Hom.: 2742 AF XY: 0.0856 AC XY: 28489 AN XY: 332992

Gnomad4 AFR exome AF: 0.0223

Gnomad4 AMR exome AF: 0.0426

Gnomad4 ASJ exome AF: 0.0824

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.0449

Gnomad4 NFE exome AF: 0.0677

Gnomad4 OTH exome AF: 0.0814

GnomAD4 genome AF: 0.0620 AC: 9431 AN: 152198 Hom.: 402 Cov.: 32 AF XY: 0.0644 AC XY: 4792 AN XY: 74410

Gnomad4 AFR AF: 0.0222

Gnomad4 AMR AF: 0.0603

Gnomad4 ASJ AF: 0.0925

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.0521

Gnomad4 NFE AF: 0.0689

Gnomad4 OTH AF: 0.0706

Alfa AF: 0.0723 Hom.: 690

Bravo AF: 0.0595

Asia WGS AF: 0.152 AC: 526 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.28
DANN	Benign	0.36

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: rs1484215; hg19: chr15-74640109;