rs138968113

Variant names:

• chr4-107947411-G-A
• rs138968113
• NM_183075.3:c.1162G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_183075.3(CYP2U1):​c.1162G>A​(p.Ala388Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000762 in 1,613,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000065 (0 hom.)
• Consequence: CYP2U1 NM_183075.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 0.187
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019226342).
• BP6: Variant 4-107947411-G-A is Benign according to our data. Variant chr4-107947411-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 569856.

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.1162G>A	p.Ala388Thr	missense	Exon 3 of 5	NP_898898.1	Q7Z449-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2U1	ENST00000332884.11	TSL:1 MANE Select	c.1162G>A	p.Ala388Thr	missense	Exon 3 of 5	ENSP00000333212.6	Q7Z449-1
	CYP2U1	ENST00000508453.1	TSL:1	c.535G>A	p.Ala179Thr	missense	Exon 5 of 7	ENSP00000423667.1	E9PGH5
	CYP2U1	ENST00000908818.1		c.772G>A	p.Ala258Thr	missense	Exon 3 of 5	ENSP00000578877.1

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152076 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000155 AC: 39 AN: 251242 AF XY: 0.000133

Gnomad AFR exome AF: 0.000678

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000650 AC: 95 AN: 1461852 Hom.: 0 Cov.: 32 AF XY: 0.0000619 AC XY: 45 AN XY: 727236

African (AFR) AF: 0.000538 AC: 18 AN: 33478

American (AMR) AF: 0.000134 AC: 6 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39698

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000369 AC: 41 AN: 1111980

Other (OTH) AF: 0.0000993 AC: 6 AN: 60396

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152076 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74296

African (AFR) AF: 0.000604 AC: 25 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68000

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000893 Hom.: 0

Bravo AF: 0.000249

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000157 AC: 19

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)
-	1	-	not provided (1)
-	-	1	Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.4
DANN	Benign	0.77
DEOGEN2	Benign	0.078	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.083	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.66	N
PhyloP100		0.19
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.035
Sift	Benign	0.72	T
Sift4G	Benign	0.48	T
Polyphen		0.0040	B
Vest4		0.12
MVP		0.13
MPC		0.14
ClinPred		0.0019	T
GERP RS		-1.1
Varity_R		0.044
gMVP		0.42
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs138968113; hg19: chr4-108868567; COSMIC: COSV60548525;