4-107931607-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_183075.3(CYP2U1):c.-37G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.023 in 1,246,234 control chromosomes in the GnomAD database, including 863 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.051 (438 hom., cov: 33)
  • Exomes 𝑓: 0.019 (425 hom.)
• Consequence: CYP2U1 NM_183075.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.54

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 4-107931607-G-A is Benign according to our data. Variant chr4-107931607-G-A is described in ClinVar as [Benign]. Clinvar id is 380776.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2U1	NM_183075.3	c.-37G>A		5_prime_UTR_variant	1/5	ENST00000332884.11
CYP2U1-AS1	NR_125929.1	n.149+364C>T		intron_variant, non_coding_transcript_variant
LOC107986298	XR_001741784.2	n.205-21058C>T		intron_variant, non_coding_transcript_variant
LOC124900751	XR_007058221.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2U1	ENST00000332884.11	c.-37G>A		5_prime_UTR_variant	1/5	1	NM_183075.3	P1
CYP2U1-AS1	ENST00000656249.1	n.81-21058C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0511 AC: 7767 AN: 152118 Hom.: 432 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0297

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00637

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.0178

Gnomad MID AF: 0.0256

Gnomad NFE AF: 0.0154

Gnomad OTH AF: 0.0478

GnomAD3 exomes AF: 0.0188 AC: 268 AN: 14222 Hom.: 10 AF XY: 0.0151 AC XY: 123 AN XY: 8136

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.0229

Gnomad ASJ exome AF: 0.00714

Gnomad EAS exome AF: 0.000627

Gnomad SAS exome AF: 0.00448

Gnomad FIN exome AF: 0.00221

Gnomad NFE exome AF: 0.00959

Gnomad OTH exome AF: 0.0225

GnomAD4 exome AF: 0.0191 AC: 20870 AN: 1094008 Hom.: 425 Cov.: 30 AF XY: 0.0183 AC XY: 9530 AN XY: 519634

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.0269

Gnomad4 ASJ exome AF: 0.00947

Gnomad4 EAS exome AF: 0.00719

Gnomad4 SAS exome AF: 0.0196

Gnomad4 FIN exome AF: 0.0182

Gnomad4 NFE exome AF: 0.0160

Gnomad4 OTH exome AF: 0.0271

GnomAD4 genome AF: 0.0512 AC: 7801 AN: 152226 Hom.: 438 Cov.: 33 AF XY: 0.0497 AC XY: 3698 AN XY: 74426

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0296

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.00639

Gnomad4 SAS AF: 0.0182

Gnomad4 FIN AF: 0.0178

Gnomad4 NFE AF: 0.0154

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.00718 Hom.: 3

Bravo AF: 0.0561

Asia WGS AF: 0.0250 AC: 85 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 04, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.67
Dann	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs112053024; hg19: chr4-108852763;