4-107931703-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1

The NM_183075.3(CYP2U1):c.60C>T(p.Leu20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000288 in 1,348,056 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

CYP2U1
NM_183075.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -1.59

Variant links:

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 links:

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

CYP2U1-AS1 links:

LOC107986298 (HGNC:):

LOC107986298 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 4-107931703-C-T is Benign according to our data. Variant chr4-107931703-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 695845.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BP7

Synonymous conserved (PhyloP=-1.59 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00158 (240/151998) while in subpopulation AFR AF= 0.00549 (228/41530). AF 95% confidence interval is 0.00491. There are 1 homozygotes in gnomad4. There are 115 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CYP2U1	NM_183075.3 linkuse as main transcript	c.60C>T	p.Leu20=	synonymous_variant	1/5	ENST00000332884.11
CYP2U1-AS1	NR_125929.1 linkuse as main transcript	n.149+268G>A		intron_variant, non_coding_transcript_variant
LOC107986298	XR_001741784.2 linkuse as main transcript	n.205-21154G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2U1	ENST00000332884.11 linkuse as main transcript	c.60C>T	p.Leu20=	synonymous_variant	1/5	1	NM_183075.3	P1	Q7Z449-1
CYP2U1-AS1	ENST00000656249.1 linkuse as main transcript	n.81-21154G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00158

AC:

240

AN:

151892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00551

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000121

AC:

AN:

8254

Hom.:

AF XY:

0.00

AC XY:

AN XY:

5120

show subpopulations

Gnomad AFR exome

AF:

0.00658

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000124

AC:

148

AN:

1196058

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

579810

show subpopulations

Gnomad4 AFR exome

AF:

0.00559

Gnomad4 AMR exome

AF:

0.000297

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000101

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.00158

AC:

240

AN:

151998

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

115

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00549

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00173

Hom.:

Bravo

AF:

0.00186

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Dec 01, 2018

- -

Spastic paraplegia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 21, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

Cadd

Benign

2.7

Dann

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over