NM_000778.4:c.1468C>T

Variant names:

• chr1-46930207-G-A
• rs1399172771
• NM_000778.4:c.1468C>T

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.1468C>T​(p.Pro490Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP4A11 NM_000778.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.305
• Publications: 1 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=0.10189268).

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.1468C>T	p.Pro490Ser	missense	Exon 12 of 12	NP_000769.2	Q02928-1
	CYP4A11	NM_001319155.2		c.1372C>T	p.Pro458Ser	missense	Exon 12 of 12	NP_001306084.1
	CYP4A11	NM_001363587.2		c.1174C>T	p.Pro392Ser	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.1468C>T	p.Pro490Ser	missense	Exon 12 of 12	ENSP00000311095.4	Q02928-1
	CYP4A11	ENST00000909039.1		c.1579C>T	p.Pro527Ser	missense	Exon 12 of 12	ENSP00000579098.1
	CYP4A11	ENST00000909036.1		c.1492C>T	p.Pro498Ser	missense	Exon 12 of 12	ENSP00000579095.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461848 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727226

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111980

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.32
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Benign	0.89
DEOGEN2	Uncertain	0.49	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		0.30
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.13
Sift	Benign	0.53	T
Sift4G	Benign	0.40	T
Polyphen		0.11	B
Vest4		0.058
MutPred		0.37		Gain of MoRF binding (P = 0.0459)
MVP		0.55
MPC		0.080
ClinPred		0.90	D
GERP RS		2.3
Varity_R		0.17
gMVP		0.50
Mutation Taster		=93/7	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: rs1399172771; hg19: chr1-47395879;