rs2229188

Variant names:

• chr7-92134309-A-G
• rs2229188
• NM_000786.4:c.56T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000786.4(CYP51A1):​c.56T>C​(p.Val19Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,450,716 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CYP51A1 NM_000786.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.87
• Publications: 9 publications found

Genes affected

CYP51A1 (HGNC:2649): (cytochrome P450 family 51 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 endoplasmic reticulum protein participates in the synthesis of cholesterol by catalyzing the removal of the 14alpha-methyl group from lanosterol. Homologous genes are found in all three eukaryotic phyla, fungi, plants, and animals, suggesting that this is one of the oldest cytochrome P450 genes. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

CYP51A1 Gene-Disease associations (from GenCC):

• cataract

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P

ENSG00000289027 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23139355).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000786.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP51A1	NM_000786.4	MANE Select	c.56T>C	p.Val19Ala	missense	Exon 1 of 10	NP_000777.1
	CYP51A1	NM_001146152.2		c.-124+357T>C		intron	N/A	NP_001139624.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP51A1	ENST00000003100.13	TSL:1 MANE Select	c.56T>C	p.Val19Ala	missense	Exon 1 of 10	ENSP00000003100.8
	ENSG00000289027	ENST00000692281.1		c.2026-2437T>C		intron	N/A	ENSP00000510568.1
	ENSG00000285772	ENST00000435873.1	TSL:4	c.25-2437T>C		intron	N/A	ENSP00000412536.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000428 AC: 1 AN: 233832 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000298

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450716 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 720160

African (AFR) AF: 0.00 AC: 0 AN: 33078

American (AMR) AF: 0.0000227 AC: 1 AN: 44114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25824

East Asian (EAS) AF: 0.00 AC: 0 AN: 39104

South Asian (SAS) AF: 0.00 AC: 0 AN: 85584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52680

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104876

Other (OTH) AF: 0.00 AC: 0 AN: 59728

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.0092
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.68	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.97	T
PhyloP100		4.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.096
Sift	Uncertain	0.011	D
Sift4G	Benign	0.26	T
Vest4		0.36
MVP		0.73
MPC		0.23
ClinPred		0.79	D
GERP RS		4.7
PromoterAI		-0.033	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
gMVP		0.67
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2229188; hg19: chr7-91763623;