4-107932139-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_183075.3(CYP2U1):c.490+6C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0195 in 1,600,114 control chromosomes in the GnomAD database, including 354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (23 hom., cov: 33)
  • Exomes 𝑓: 0.020 (331 hom.)
• Consequence: CYP2U1 NM_183075.3 splice_donor_region, intron
• Scores: Splicing: ADA: 0.0002490
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.763

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 4-107932139-C-T is Benign according to our data. Variant chr4-107932139-C-T is described in ClinVar as [Benign]. Clinvar id is 242188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0148 (2256/152284) while in subpopulation NFE AF= 0.0232 (1575/68024). AF 95% confidence interval is 0.0222. There are 23 homozygotes in gnomad4. There are 1113 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2U1	NM_183075.3	c.490+6C>T		splice_donor_region_variant, intron_variant		ENST00000332884.11
LOC107986298	XR_001741784.2	n.205-21590G>A		intron_variant, non_coding_transcript_variant
CYP2U1-AS1	NR_125929.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2U1	ENST00000332884.11	c.490+6C>T		splice_donor_region_variant, intron_variant		1	NM_183075.3	P1
CYP2U1-AS1	ENST00000656249.1	n.81-21590G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2257 AN: 152168 Hom.: 23 Cov.: 33

Gnomad AFR AF: 0.00359

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.0243

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0232

Gnomad OTH AF: 0.0163

GnomAD3 exomes AF: 0.0166 AC: 3648 AN: 219440 Hom.: 47 AF XY: 0.0169 AC XY: 2038 AN XY: 120904

Gnomad AFR exome AF: 0.00291

Gnomad AMR exome AF: 0.00863

Gnomad ASJ exome AF: 0.0106

Gnomad EAS exome AF: 0.0000594

Gnomad SAS exome AF: 0.00582

Gnomad FIN exome AF: 0.0287

Gnomad NFE exome AF: 0.0252

Gnomad OTH exome AF: 0.0183

GnomAD4 exome AF: 0.0200 AC: 28899 AN: 1447830 Hom.: 331 Cov.: 31 AF XY: 0.0198 AC XY: 14246 AN XY: 719108

Gnomad4 AFR exome AF: 0.00316

Gnomad4 AMR exome AF: 0.00854

Gnomad4 ASJ exome AF: 0.00948

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00613

Gnomad4 FIN exome AF: 0.0291

Gnomad4 NFE exome AF: 0.0225

Gnomad4 OTH exome AF: 0.0180

GnomAD4 genome AF: 0.0148 AC: 2256 AN: 152284 Hom.: 23 Cov.: 33 AF XY: 0.0149 AC XY: 1113 AN XY: 74460

Gnomad4 AFR AF: 0.00356

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.0243

Gnomad4 NFE AF: 0.0232

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0208 Hom.: 16

Bravo AF: 0.0133

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Spastic paraplegia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 02, 2017

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. -

Hereditary spastic paraplegia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Dec 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
Cadd	Benign	16
Dann	Benign	0.94

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00025
dbscSNV1_RF	Benign	0.010
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: rs147612190; hg19: chr4-108853295;