1-46935752-A-T

Position:

• chr1-46935752-A-T

Variant summary

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

The NM_000778.4(CYP4A11):​c.511-105T>A 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 1,524,684 control chromosomes in the GnomAD database, including 433,753 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 0.65 (34632 hom., cov: 33)
  • Exomes 𝑓: 0.76 (399121 hom.)
• Consequence: CYP4A11 NM_000778.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655

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=-0.98).
• 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.511-105T>A		intron_variant		ENST00000310638.9	NP_000769.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4A11	ENST00000310638.9	c.511-105T>A		intron_variant		1	NM_000778.4	ENSP00000311095.4
CYP4A11	ENST00000465874.5	n.511-105T>A		intron_variant		2		ENSP00000476368.1

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99563 AN: 151954 Hom.: 34631 Cov.: 33

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.683

GnomAD4 exome AF: 0.757 AC: 1038806 AN: 1372612 Hom.: 399121 AF XY: 0.754 AC XY: 507593 AN XY: 673040

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.673

Gnomad4 ASJ exome AF: 0.779

Gnomad4 EAS exome AF: 0.494

Gnomad4 SAS exome AF: 0.619

Gnomad4 FIN exome AF: 0.765

Gnomad4 NFE exome AF: 0.790

Gnomad4 OTH exome AF: 0.735

GnomAD4 genome AF: 0.655 AC: 99574 AN: 152072 Hom.: 34632 Cov.: 33 AF XY: 0.652 AC XY: 48472 AN XY: 74322

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.775

Gnomad4 EAS AF: 0.513

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.758

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.689

Alfa AF: 0.641 Hom.: 2230

Bravo AF: 0.643

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.31
DANN	Benign	0.46

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: rs2269231; hg19: chr1-47401424;