chr7-92134309-A-G

Position:

• chr7-92134309-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP51A1	NM_000786.4	c.56T>C	p.Val19Ala	missense_variant	1/10	ENST00000003100.13
CYP51A1	NM_001146152.2	c.-124+357T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP51A1	ENST00000003100.13	c.56T>C	p.Val19Ala	missense_variant	1/10	1	NM_000786.4	P1
CYP51A1	ENST00000691309.1	c.56T>C	p.Val19Ala	missense_variant	1/10
CYP51A1	ENST00000450723.5	c.-124+357T>C		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000428 AC: 1 AN: 233832 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 127612

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 SAS 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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000227

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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
MutationTaster	Benign	1.0	D;N
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
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
gMVP		0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs2229188; hg19: chr7-91763623;