4-107931574-C-T

Position:

• chr4-107931574-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_183075.3(CYP2U1):​c.-70C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00481 in 1,212,530 control chromosomes in the GnomAD database, including 188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (117 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (71 hom.)
• Consequence: CYP2U1 NM_183075.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.49

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]

LOC124900751 (HGNC:):

CYP2U1-AS1 (HGNC:54817): (CYP2U1 and SGMS2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 4-107931574-C-T is Benign according to our data. Variant chr4-107931574-C-T is described in ClinVar as [Benign]. Clinvar id is 1242157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2U1	NM_183075.3	c.-70C>T		5_prime_UTR_variant	1/5	ENST00000332884.11	NP_898898.1
LOC124900751	XR_007058221.1	n.12G>A		non_coding_transcript_exon_variant	1/2
CYP2U1-AS1	NR_125929.1	n.149+397G>A		intron_variant, non_coding_transcript_variant
LOC107986298	XR_001741784.2	n.205-21025G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2U1	ENST00000332884.11	c.-70C>T		5_prime_UTR_variant	1/5	1	NM_183075.3	ENSP00000333212	P1
CYP2U1-AS1	ENST00000656249.1	n.81-21025G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0226 AC: 3445 AN: 152192 Hom.: 118 Cov.: 33

Gnomad AFR AF: 0.0772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00988

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.00224 AC: 2376 AN: 1060226 Hom.: 71 Cov.: 25 AF XY: 0.00201 AC XY: 1009 AN XY: 501238

Gnomad4 AFR exome AF: 0.0755

Gnomad4 AMR exome AF: 0.00936

Gnomad4 ASJ exome AF: 0.00197

Gnomad4 EAS exome AF: 0.0000400

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000473

Gnomad4 NFE exome AF: 0.000306

Gnomad4 OTH exome AF: 0.00712

GnomAD4 genome AF: 0.0227 AC: 3457 AN: 152304 Hom.: 117 Cov.: 33 AF XY: 0.0211 AC XY: 1574 AN XY: 74474

Gnomad4 AFR AF: 0.0773

Gnomad4 AMR AF: 0.00986

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.000860 Hom.: 2

Bravo AF: 0.0263

Asia WGS AF: 0.00376 AC: 13 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 08, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.2
DANN	Benign	0.88

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: rs139667669; hg19: chr4-108852730;