1-46934207-T-G

Position:

• chr1-46934207-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000778.4(CYP4A11):​c.1057A>C​(p.Ser353Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S353G) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 29)
• Consequence: CYP4A11 NM_000778.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

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]

CYP4A11 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33354634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4A11	NM_000778.4	c.1057A>C	p.Ser353Arg	missense_variant	8/12	ENST00000310638.9	NP_000769.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4A11	ENST00000310638.9	c.1057A>C	p.Ser353Arg	missense_variant	8/12	1	NM_000778.4	ENSP00000311095.4
CYP4A11	ENST00000465874.5	n.609-202A>C		intron_variant		2		ENSP00000476368.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152042 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152042 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 74250

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	3.2
DANN	Benign	0.95
DEOGEN2	Benign	0.21	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.11	T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	2.0	M;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.082
Sift	Benign	0.26	T;T;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.0030	B;.;.
Vest4		0.21
MutPred		0.43		Loss of glycosylation at S353 (P = 0.0357);.;Loss of glycosylation at S353 (P = 0.0357);
MVP		0.48
MPC		0.072
ClinPred		0.21	T
GERP RS		1.1
Varity_R		0.23
gMVP		0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs3899049; hg19: chr1-47399879;