1-46938514-T-C

Position:

• chr1-46938514-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000778.4(CYP4A11):​c.196-377A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,256 control chromosomes in the GnomAD database, including 2,010 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2010 hom., cov: 33)
• Consequence: CYP4A11 NM_000778.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4A11	NM_000778.4	c.196-377A>G		intron_variant		ENST00000310638.9	NP_000769.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4A11	ENST00000310638.9	c.196-377A>G		intron_variant		1	NM_000778.4	ENSP00000311095.4
CYP4A11	ENST00000465874.5	n.196-377A>G		intron_variant		2		ENSP00000476368.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23908 AN: 152138 Hom.: 2007 Cov.: 33

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.150

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.157 AC: 23925 AN: 152256 Hom.: 2010 Cov.: 33 AF XY: 0.159 AC XY: 11807 AN XY: 74428

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.148

Alfa AF: 0.135 Hom.: 2066

Bravo AF: 0.156

Asia WGS AF: 0.244 AC: 848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.9
DANN	Benign	0.77

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: rs9332998; hg19: chr1-47404186; COSMIC: COSV60222807; COSMIC: COSV60222807;