4-107931653-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_183075.3(CYP2U1):c.10C>T(p.Pro4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00063 in 1,259,394 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P4L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0033 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00026 (4 hom.)
• Consequence: CYP2U1 NM_183075.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.92

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022039711).
• BP6: Variant 4-107931653-C-T is Benign according to our data. Variant chr4-107931653-C-T is described in ClinVar as [Benign]. Clinvar id is 695323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00331 (503/151836) while in subpopulation AFR AF= 0.0118 (488/41472). AF 95% confidence interval is 0.0109. There are 3 homozygotes in gnomad4. There are 252 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2U1	NM_183075.3	c.10C>T	p.Pro4Ser	missense_variant	1/5	ENST00000332884.11
CYP2U1-AS1	NR_125929.1	n.149+318G>A		intron_variant, non_coding_transcript_variant
LOC107986298	XR_001741784.2	n.205-21104G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2U1	ENST00000332884.11	c.10C>T	p.Pro4Ser	missense_variant	1/5	1	NM_183075.3	P1
CYP2U1-AS1	ENST00000656249.1	n.81-21104G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00331 AC: 502 AN: 151728 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

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: 0.0000147

Gnomad OTH AF: 0.000959

GnomAD3 exomes AF: 0.00235 AC: 3 AN: 1274 Hom.: 0 AF XY: 0.00135 AC XY: 1 AN XY: 740

Gnomad AFR exome AF: 0.0484

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: 0.000263 AC: 291 AN: 1107558 Hom.: 4 Cov.: 30 AF XY: 0.000239 AC XY: 126 AN XY: 527768

Gnomad4 AFR exome AF: 0.0113

Gnomad4 AMR exome AF: 0.000977

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: 0.00000320

Gnomad4 OTH exome AF: 0.000539

GnomAD4 genome AF: 0.00331 AC: 503 AN: 151836 Hom.: 3 Cov.: 33 AF XY: 0.00340 AC XY: 252 AN XY: 74212

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.000786

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.00291 Hom.: 0

Bravo AF: 0.00354

ESP6500AA AF: 0.00136 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000656 AC: 37

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

CYP2U1: PP2, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	0.067
Dann	Benign	0.94
DEOGEN2	Benign	0.080	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.039
Sift	Benign	0.51	T
Sift4G	Benign	0.29	T
Polyphen		0.0010	B
Vest4		0.14
MVP		0.17
MPC		1.5
ClinPred		0.022	T
GERP RS		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.023
gMVP		0.21

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: rs371029660; hg19: chr4-108852809;