4-107932139-C-T

Variant names:

• chr4-107932139-C-T
• rs147612190
• NM_183075.3:c.490+6C>T

Variant summary

Our verdict is Benign. The variant received -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 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. 3/3 splice prediction tools predict no significant impact on normal splicing. 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_region, intron
• Scores: Splicing: ADA: 0.0002490
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.763
• Publications: 5 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183075.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2U1	NM_183075.3	MANE Select	c.490+6C>T		splice_region intron	N/A	NP_898898.1
	CYP2U1-AS1	NR_125929.1		n.-20G>A		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2U1	ENST00000332884.11	TSL:1 MANE Select	c.490+6C>T		splice_region intron	N/A	ENSP00000333212.6
	CYP2U1	ENST00000508453.1	TSL:1	c.-336+6C>T		splice_region intron	N/A	ENSP00000423667.1
	CYP2U1	ENST00000513302.1	TSL:1	n.549+6C>T		splice_region intron	N/A

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

GnomAD2 exomes AF: 0.0166 AC: 3648 AN: 219440 AF XY: 0.0169

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 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

African (AFR) AF: 0.00316 AC: 105 AN: 33246

American (AMR) AF: 0.00854 AC: 372 AN: 43550

Ashkenazi Jewish (ASJ) AF: 0.00948 AC: 244 AN: 25744

East Asian (EAS) AF: 0.00 AC: 0 AN: 39168

South Asian (SAS) AF: 0.00613 AC: 516 AN: 84134

European-Finnish (FIN) AF: 0.0291 AC: 1454 AN: 50008

Middle Eastern (MID) AF: 0.0337 AC: 191 AN: 5672

European-Non Finnish (NFE) AF: 0.0225 AC: 24937 AN: 1106428

Other (OTH) AF: 0.0180 AC: 1080 AN: 59880

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

African (AFR) AF: 0.00356 AC: 148 AN: 41580

American (AMR) AF: 0.0101 AC: 154 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4828

European-Finnish (FIN) AF: 0.0243 AC: 258 AN: 10606

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0232 AC: 1575 AN: 68024

Other (OTH) AF: 0.0161 AC: 34 AN: 2112

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Spastic paraplegia Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Jun 02, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Dec 22, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Benign	0.94
PhyloP100		0.76
Mutation Taster		=83/17	polymorphism (auto)

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

Other links and lift over

dbSNP: rs147612190; hg19: chr4-108853295;