rs1843090

Variant names:

• chr15-74350693-A-G
• rs1843090
• NM_000781.3:c.270-2638T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• Congenital adrenal insufficiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency

  Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• inherited isolated adrenal insufficiency due to partial CYP11A1 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000293337 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000781.3. 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
	CYP11A1	NM_000781.3	MANE Select	c.270-2638T>C		intron	N/A	NP_000772.2	P05108-1
	CYP11A1	NM_001099773.2		c.-205-2638T>C		intron	N/A	NP_001093243.1	P05108-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP11A1	ENST00000268053.11	TSL:1 MANE Select	c.270-2638T>C		intron	N/A	ENSP00000268053.6	P05108-1
	CYP11A1	ENST00000950903.1		c.270-2638T>C		intron	N/A	ENSP00000620962.1
	CYP11A1	ENST00000950905.1		c.270-2638T>C		intron	N/A	ENSP00000620964.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.500 AC: 3 AN: 6

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.875 AC: 7 AN: 8

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.679 AC: 53 AN: 78

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.545 AC: 22589 AN: 41432

American (AMR) AF: 0.664 AC: 10145 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2314 AN: 3468

East Asian (EAS) AF: 0.547 AC: 2829 AN: 5168

South Asian (SAS) AF: 0.549 AC: 2642 AN: 4814

European-Finnish (FIN) AF: 0.762 AC: 8050 AN: 10560

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.710 AC: 48227 AN: 67954

Other (OTH) AF: 0.626 AC: 1319 AN: 2106

Alfa AF: 0.685 Hom.: 61872

Bravo AF: 0.641

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.49
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs1843090; hg19: chr15-74643034;