rs3890011

Positions:

• chr1-46933071-G-C

Variant summary

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

The NM_000778.4(CYP4A11):​c.1223-24C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 1,613,560 control chromosomes in the GnomAD database, including 458,757 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 0.66 (34639 hom., cov: 31)
  • Exomes 𝑓: 0.76 (424118 hom.)
• Consequence: CYP4A11 NM_000778.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4A11	NM_000778.4	c.1223-24C>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.1223-24C>G		intron_variant		1	NM_000778.4	ENSP00000311095.4
CYP4A11	ENST00000465874.5	n.*21-24C>G		intron_variant		2		ENSP00000476368.1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99585 AN: 151902 Hom.: 34638 Cov.: 31

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.766

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.685

GnomAD3 exomes AF: 0.707 AC: 177311 AN: 250836 Hom.: 64412 AF XY: 0.710 AC XY: 96171 AN XY: 135508

Gnomad AFR exome AF: 0.405

Gnomad AMR exome AF: 0.694

Gnomad ASJ exome AF: 0.776

Gnomad EAS exome AF: 0.526

Gnomad SAS exome AF: 0.627

Gnomad FIN exome AF: 0.768

Gnomad NFE exome AF: 0.785

Gnomad OTH exome AF: 0.743

GnomAD4 exome AF: 0.756 AC: 1105572 AN: 1461540 Hom.: 424118 Cov.: 57 AF XY: 0.754 AC XY: 548091 AN XY: 727042

Gnomad4 AFR exome AF: 0.393

Gnomad4 AMR exome AF: 0.690

Gnomad4 ASJ exome AF: 0.779

Gnomad4 EAS exome AF: 0.498

Gnomad4 SAS exome AF: 0.624

Gnomad4 FIN exome AF: 0.767

Gnomad4 NFE exome AF: 0.790

Gnomad4 OTH exome AF: 0.736

GnomAD4 genome AF: 0.655 AC: 99596 AN: 152020 Hom.: 34639 Cov.: 31 AF XY: 0.652 AC XY: 48485 AN XY: 74324

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.758

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.691

Alfa AF: 0.728 Hom.: 7602

Bravo AF: 0.643

Asia WGS AF: 0.578 AC: 2009 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.2
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3890011; hg19: chr1-47398743; COSMIC: COSV60222498; COSMIC: COSV60222498;