NM_183075.3:c.490+2487G>A

Variant names:

• chr4-107934620-G-A
• rs2131463
• NM_183075.3:c.490+2487G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183075.3(CYP2U1):​c.490+2487G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,862 control chromosomes in the GnomAD database, including 11,892 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 0.39 (11892 hom., cov: 31)
• Consequence: CYP2U1 NM_183075.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• Publications: 9 publications found

Genes affected

CYP2U1 (HGNC:20582): (cytochrome P450 family 2 subfamily U member 1) 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 enzyme is a hydroxylase that metabolizes arachidonic acid, docosahexaenoic acid, and other long chain fatty acids. [provided by RefSeq, Jul 2008]

CYP2U1-AS1 (HGNC:54817): (CYP2U1 and SGMS2 antisense RNA 1)

LOC107986298 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2U1	NM_183075.3	c.490+2487G>A		intron_variant	Intron 1 of 4	ENST00000332884.11	NP_898898.1
CYP2U1	XM_005262717.2	c.544+2433G>A		intron_variant	Intron 1 of 4		XP_005262774.1
CYP2U1	XM_005262720.2	c.490+2487G>A		intron_variant	Intron 1 of 3		XP_005262777.1
LOC107986298	XR_001741784.2	n.205-24071C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2U1	ENST00000332884.11	c.490+2487G>A		intron_variant	Intron 1 of 4	1	NM_183075.3	ENSP00000333212.6

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58865 AN: 151744 Hom.: 11883 Cov.: 31

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.388 AC: 58902 AN: 151862 Hom.: 11892 Cov.: 31 AF XY: 0.397 AC XY: 29430 AN XY: 74224

African (AFR) AF: 0.435 AC: 17998 AN: 41388

American (AMR) AF: 0.443 AC: 6761 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 816 AN: 3466

East Asian (EAS) AF: 0.683 AC: 3525 AN: 5158

South Asian (SAS) AF: 0.473 AC: 2278 AN: 4812

European-Finnish (FIN) AF: 0.398 AC: 4186 AN: 10524

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22233 AN: 67942

Other (OTH) AF: 0.351 AC: 740 AN: 2108

Alfa AF: 0.338 Hom.: 15628

Bravo AF: 0.394

Asia WGS AF: 0.516 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.0
DANN	Benign	0.83
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2131463; hg19: chr4-108855776;