rs8727

Positions:

• chr4-107952129-T-C
• chr4-107952129-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000332884.11(CYP2U1):​c.*1706T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,266 control chromosomes in the GnomAD database, including 2,808 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (2808 hom., cov: 32)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: CYP2U1 ENST00000332884.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.697

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2U1	NM_183075.3	c.*1706T>C		3_prime_UTR_variant	5/5	ENST00000332884.11	NP_898898.1
LOC107986298	XR_001741784.2	n.204+26591A>G		intron_variant, non_coding_transcript_variant
CYP2U1	XM_005262717.2	c.*1706T>C		3_prime_UTR_variant	5/5		XP_005262774.1
CYP2U1	XM_005262720.2	c.*1706T>C		3_prime_UTR_variant	4/4		XP_005262777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2U1	ENST00000332884.11	c.*1706T>C		3_prime_UTR_variant	5/5	1	NM_183075.3	ENSP00000333212	P1
CYP2U1-AS1	ENST00000656249.1	n.80+26591A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28243 AN: 152130 Hom.: 2811 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0225

Gnomad SAS AF: 0.0721

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.199

GnomAD4 exome AF: 0.333 AC: 6 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.313 AC XY: 5 AN XY: 16

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.185 AC: 28231 AN: 152248 Hom.: 2808 Cov.: 32 AF XY: 0.185 AC XY: 13736 AN XY: 74432

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.0225

Gnomad4 SAS AF: 0.0714

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.197

Alfa AF: 0.198 Hom.: 3235

Bravo AF: 0.180

Asia WGS AF: 0.0580 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.8
DANN	Benign	0.76

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: rs8727; hg19: chr4-108873285;