chr4-107931622-C-A

Variant names:

• chr4-107931622-C-A
• rs776990308
• NM_183075.3:c.-22C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_183075.3(CYP2U1):​c.-22C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP2U1 NM_183075.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.669
• Publications: 0 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 4-107931622-C-A is Benign according to our data. Variant chr4-107931622-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 389852.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-22C>A		5_prime_UTR	Exon 1 of 5	NP_898898.1	Q7Z449-1
	CYP2U1-AS1	NR_125929.1		n.149+349G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2U1	ENST00000332884.11	TSL:1 MANE Select	c.-22C>A		5_prime_UTR	Exon 1 of 5	ENSP00000333212.6	Q7Z449-1
	CYP2U1	ENST00000508453.1	TSL:1	c.-847C>A		5_prime_UTR	Exon 1 of 7	ENSP00000423667.1	E9PGH5
	CYP2U1	ENST00000513302.1	TSL:1	n.38C>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1099048 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 522576

African (AFR) AF: 0.00 AC: 0 AN: 23104

American (AMR) AF: 0.00 AC: 0 AN: 8560

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14018

East Asian (EAS) AF: 0.00 AC: 0 AN: 26676

South Asian (SAS) AF: 0.00 AC: 0 AN: 23436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2922

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 933640

Other (OTH) AF: 0.00 AC: 0 AN: 44120

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.2
DANN	Benign	0.59
PhyloP100		-0.67
PromoterAI		0.18	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs776990308; hg19: chr4-108852778;