chr4-107931696-CGCGCCTCCTGCGT-C

Variant names:

• chr4-107931696-CGCGCCTCCTGCGT-C
• NM_183075.3:c.61_73delCTGCGTGCGCCTC

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_183075.3(CYP2U1):​c.61_73delCTGCGTGCGCCTC​(p.Leu21TrpfsTer19) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000168 in 1,188,168 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: CYP2U1 NM_183075.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.35
• 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_pathogenic. The variant received 9 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 50 pathogenic variants in the truncated region.
• PP5: Variant 4-107931696-CGCGCCTCCTGCGT-C is Pathogenic according to our data. Variant chr4-107931696-CGCGCCTCCTGCGT-C is described in ClinVar as Pathogenic. ClinVar VariationId is 39502.Status of the report is no_assertion_criteria_provided, 0 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.61_73delCTGCGTGCGCCTC	p.Leu21TrpfsTer19	frameshift	Exon 1 of 5	NP_898898.1	Q7Z449-1
	CYP2U1-AS1	NR_125929.1		n.149+262_149+274delACGCAGGAGGCGC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2U1	ENST00000332884.11	TSL:1 MANE Select	c.61_73delCTGCGTGCGCCTC	p.Leu21TrpfsTer19	frameshift	Exon 1 of 5	ENSP00000333212.6	Q7Z449-1
	CYP2U1	ENST00000508453.1	TSL:1	c.-765_-753delCTGCGTGCGCCTC		5_prime_UTR	Exon 1 of 7	ENSP00000423667.1	E9PGH5
	CYP2U1	ENST00000513302.1	TSL:1	n.120_132delCTGCGTGCGCCTC		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000168 AC: 2 AN: 1188168 Hom.: 0 AF XY: 0.00000174 AC XY: 1 AN XY: 575176

African (AFR) AF: 0.00 AC: 0 AN: 23314

American (AMR) AF: 0.00 AC: 0 AN: 9658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16314

East Asian (EAS) AF: 0.00 AC: 0 AN: 26812

South Asian (SAS) AF: 0.00 AC: 0 AN: 44710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3320

European-Non Finnish (NFE) AF: 0.00000203 AC: 2 AN: 987010

Other (OTH) AF: 0.00 AC: 0 AN: 48654

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Hereditary spastic paraplegia 56 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=10/190	disease causing (fs/PTC)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr4-108852852;