1-46930207-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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

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=0.10189268).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4A11	NM_000778.4	c.1468C>T	p.Pro490Ser	missense_variant	Exon 12 of 12	ENST00000310638.9	NP_000769.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4A11	ENST00000310638.9	c.1468C>T	p.Pro490Ser	missense_variant	Exon 12 of 12	1	NM_000778.4	ENSP00000311095.4

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

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

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.: 30

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1468C>T (p.P490S) alteration is located in exon 12 (coding exon 12) of the CYP4A11 gene. This alteration results from a C to T substitution at nucleotide position 1468, causing the proline (P) at amino acid position 490 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Pathogenic	2.9	M;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-4.1	D;D;.
REVEL	Benign	0.13
Sift	Benign	0.53	T;T;.
Sift4G	Benign	0.40	T;T;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

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: rs1399172771; hg19: chr1-47395879;