rs773841071

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate

The ENST00000508453.1(CYP2U1):c.-825A>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000905 in 1,105,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 9.0e-7 ( 0 hom. )

Consequence

CYP2U1
ENST00000508453.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.17

Publications

2 publications found

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 was made for transcript

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.992

PP5

Variant 4-107931644-A-C is Pathogenic according to our data. Variant chr4-107931644-A-C is described in ClinVar as Pathogenic. ClinVar VariationId is 989059.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000508453.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2U1	NM_183075.3	MANE Select	c.1A>C	p.Met1?	initiator_codon	Exon 1 of 5	NP_898898.1	Q7Z449-1
	CYP2U1-AS1	NR_125929.1		n.149+327T>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYP2U1	ENST00000508453.1	TSL:1	c.-825A>C		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000423667.1	E9PGH5
CYP2U1	ENST00000332884.11	TSL:1 MANE Select	c.1A>C	p.Met1?	initiator_codon	Exon 1 of 5	ENSP00000333212.6	Q7Z449-1
CYP2U1	ENST00000508453.1	TSL:1	c.-825A>C		5_prime_UTR	Exon 1 of 7	ENSP00000423667.1	E9PGH5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

3572

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

9.05e-7

AC:

AN:

1105060

Hom.:

Cov.:

AF XY:

0.00000190

AC XY:

AN XY:

526400

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22852

American (AMR)

AF:

0.00

AC:

AN:

8242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14218

East Asian (EAS)

AF:

0.00

AC:

AN:

26274

South Asian (SAS)

AF:

0.00

AC:

AN:

26010

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23068

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2944

European-Non Finnish (NFE)

AF:

0.00000107

AC:

AN:

937122

Other (OTH)

AF:

0.00

AC:

AN:

44330

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000136

AC:

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary spastic paraplegia 56 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.088

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

1.0

MetaRNN

Pathogenic

0.99

MetaSVM

Benign

-0.28

PhyloP100

2.2

PROVEAN

Benign

-0.38

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.70

Vest4

0.91

MutPred

0.99

Gain of catalytic residue at M1 (P = 0.1148)

MVP

0.82

ClinPred

0.99

GERP RS

4.2

PromoterAI

-0.22

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.92

gMVP

0.30

Mutation Taster

=20/180

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over