rs11638442

chr15-74342558-C-Gchr15-74342558-C-T

Variant summary

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

The NM_000781.3(CYP11A1):c.990+419G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,964 control chromosomes in the GnomAD database, including 19,353 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 0.48 (19353 hom., cov: 31)
• Consequence: CYP11A1 NM_000781.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP11A1	NM_000781.3	c.990+419G>C		intron_variant		ENST00000268053.11
CYP11A1	NM_001099773.2	c.516+419G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP11A1	ENST00000268053.11	c.990+419G>C		intron_variant		1	NM_000781.3	P1
CYP11A1	ENST00000358632.8	c.516+419G>C		intron_variant		2
CYP11A1	ENST00000566674.5	c.516+419G>C		intron_variant		5
CYP11A1	ENST00000435365.5	c.990+419G>C		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72699 AN: 151846 Hom.: 19355 Cov.: 31

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.460

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.479 AC: 72727 AN: 151964 Hom.: 19353 Cov.: 31 AF XY: 0.472 AC XY: 35041 AN XY: 74286

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.456

Alfa AF: 0.437 Hom.: 1453

Bravo AF: 0.465

Asia WGS AF: 0.236 AC: 821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.076
Dann	Benign	0.71

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: rs11638442; hg19: chr15-74634899;