15-74345526-A-G

Position:

• chr15-74345526-A-G

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.426-283T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,646 control chromosomes in the GnomAD database, including 19,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.48 (19189 hom., cov: 31)
• Consequence: CYP11A1 NM_000781.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.400

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-74345526-A-G is Benign according to our data. Variant chr15-74345526-A-G is described in ClinVar as [Benign]. Clinvar id is 1276338.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP11A1	NM_000781.3	c.426-283T>C		intron_variant		ENST00000268053.11	NP_000772.2
CYP11A1	NM_001099773.2	c.-49-283T>C		intron_variant			NP_001093243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP11A1	ENST00000268053.11	c.426-283T>C		intron_variant		1	NM_000781.3	ENSP00000268053.6

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72175 AN: 151528 Hom.: 19191 Cov.: 31

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.476 AC: 72201 AN: 151646 Hom.: 19189 Cov.: 31 AF XY: 0.470 AC XY: 34796 AN XY: 74108

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.642

Gnomad4 NFE AF: 0.606

Gnomad4 OTH AF: 0.455

Alfa AF: 0.562 Hom.: 50993

Bravo AF: 0.461

Asia WGS AF: 0.235 AC: 818 AN: 3476

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

Apr 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.93
DANN	Benign	0.66

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: rs11632698; hg19: chr15-74637867;