rs550088634

Variant names:

• chr4-107931648-C-G
• rs550088634
• NM_183075.3:c.5C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-107931648-C-G
• chr4-107931648-C-T
• chr4-107931648-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_183075.3(CYP2U1):​c.5C>G​(p.Ser2Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000452 in 1,107,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: CYP2U1 NM_183075.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.554
• Publications: 2 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40488672).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2U1	NM_183075.3	MANE Select	c.5C>G	p.Ser2Trp	missense	Exon 1 of 5	NP_898898.1	Q7Z449-1
	CYP2U1-AS1	NR_125929.1		n.149+323G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2U1	ENST00000332884.11	TSL:1 MANE Select	c.5C>G	p.Ser2Trp	missense	Exon 1 of 5	ENSP00000333212.6	Q7Z449-1
	CYP2U1	ENST00000508453.1	TSL:1	c.-821C>G		5_prime_UTR	Exon 1 of 7	ENSP00000423667.1	E9PGH5
	CYP2U1	ENST00000513302.1	TSL:1	n.64C>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000452 AC: 5 AN: 1107090 Hom.: 0 Cov.: 30 AF XY: 0.00000569 AC XY: 3 AN XY: 527304

African (AFR) AF: 0.00 AC: 0 AN: 22824

American (AMR) AF: 0.00 AC: 0 AN: 8230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14320

East Asian (EAS) AF: 0.0000382 AC: 1 AN: 26160

South Asian (SAS) AF: 0.00 AC: 0 AN: 26354

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2960

European-Non Finnish (NFE) AF: 0.00000426 AC: 4 AN: 938522

Other (OTH) AF: 0.00 AC: 0 AN: 44520

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.095	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.42	T
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.55
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.16
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.95	P
Vest4		0.27
MutPred		0.12		Loss of phosphorylation at S2 (P = 0.0036)
MVP		0.68
MPC		2.0
ClinPred		0.48	T
GERP RS		3.3
PromoterAI		-0.20	Neutral
Varity_R		0.091
gMVP		0.29
Mutation Taster		=297/3	polymorphism

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

Other links and lift over

dbSNP: rs550088634; hg19: chr4-108852804;