1-46930162-G-C

Variant names:

• chr1-46930162-G-C
• rs765836836
• NM_000778.4:c.1513C>G

Variant summary

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

The NM_000778.4(CYP4A11):​c.1513C>G​(p.Arg505Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CYP4A11 NM_000778.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.00
• Publications: 3 publications found

Genes affected

CYP4A11 (HGNC:2642): (cytochrome P450 family 4 subfamily A member 11) 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 endoplasmic reticulum and hydroxylates medium-chain fatty acids such as laurate and myristate. Multiple transcript variants have been found for this gene. [provided by RefSeq, Jan 2016]

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=0.20424935).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000778.4. 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
	CYP4A11	NM_000778.4	MANE Select	c.1513C>G	p.Arg505Gly	missense	Exon 12 of 12	NP_000769.2	Q02928-1
	CYP4A11	NM_001319155.2		c.1417C>G	p.Arg473Gly	missense	Exon 12 of 12	NP_001306084.1
	CYP4A11	NM_001363587.2		c.1219C>G	p.Arg407Gly	missense	Exon 10 of 10	NP_001350516.1	V9GZ77

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4A11	ENST00000310638.9	TSL:1 MANE Select	c.1513C>G	p.Arg505Gly	missense	Exon 12 of 12	ENSP00000311095.4	Q02928-1
	CYP4A11	ENST00000909039.1		c.1624C>G	p.Arg542Gly	missense	Exon 12 of 12	ENSP00000579098.1
	CYP4A11	ENST00000909036.1		c.1537C>G	p.Arg513Gly	missense	Exon 12 of 12	ENSP00000579095.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251264 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

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: 0.00000547 AC: 8 AN: 1461754 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727184

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111930

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	4.0
DANN	Benign	0.94
DEOGEN2	Benign	0.31	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.5	L
PhyloP100		-3.0
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.088
Sift	Uncertain	0.029	D
Sift4G	Benign	0.14	T
Polyphen		0.20	B
Vest4		0.15
MutPred		0.62		Loss of MoRF binding (P = 0.0518)
MVP		0.47
MPC		0.11
ClinPred		0.13	T
GERP RS		-1.2
Varity_R		0.079
gMVP		0.65
Mutation Taster		=96/4	polymorphism

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: rs765836836; hg19: chr1-47395834;