1-46933825-T-C

Position:

• chr1-46933825-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.1222+121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,445,466 control chromosomes in the GnomAD database, including 16,746 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 (2027 hom., cov: 30)
  • Exomes 𝑓: 0.14 (14719 hom.)
• Consequence: CYP4A11 NM_000778.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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=-0.92).
• 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.1222+121A>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.1222+121A>G		intron_variant		1	NM_000778.4	ENSP00000311095.4
CYP4A11	ENST00000465874.5	n.*20+121A>G		intron_variant		2		ENSP00000476368.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23983 AN: 152042 Hom.: 2023 Cov.: 30

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.143 AC: 185325 AN: 1293306 Hom.: 14719 AF XY: 0.147 AC XY: 92392 AN XY: 630336

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.140

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.223

Gnomad4 SAS exome AF: 0.285

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.158 AC: 24005 AN: 152160 Hom.: 2027 Cov.: 30 AF XY: 0.160 AC XY: 11866 AN XY: 74394

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.147

Alfa AF: 0.136 Hom.: 1258

Bravo AF: 0.157

Asia WGS AF: 0.237 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.041
DANN	Benign	0.47

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: rs4660980; hg19: chr1-47399497; COSMIC: COSV60222779; COSMIC: COSV60222779;