rs200054565

Variant names:

• chr4-186191693-GC-G
• rs200054565
• NM_207352.4:c.-130delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_207352.4(CYP4V2):​c.-130delC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 869,854 control chromosomes in the GnomAD database, including 39 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (29 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (10 hom.)
• Consequence: CYP4V2 NM_207352.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -2.26
• Publications: 0 publications found

Genes affected

CYP4V2 (HGNC:23198): (cytochrome P450 family 4 subfamily V member 2) This gene encodes a member of the cytochrome P450 hemethiolate protein superfamily which are involved in oxidizing various substrates in the metabolic pathway. It is implicated in the metabolism of fatty acid precursors into n-3 polyunsaturated fatty acids. Mutations in this gene result in Bietti crystalline corneoretinal dystrophy. [provided by RefSeq, Jul 2008]

CYP4V2 Gene-Disease associations (from GenCC):

• Bietti crystalline corneoretinal dystrophy

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), Illumina, G2P

FLJ38576 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 4-186191693-GC-G is Benign according to our data. Variant chr4-186191693-GC-G is described in ClinVar as Likely_benign. ClinVar VariationId is 348293.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0103 (1572/151960) while in subpopulation AFR AF = 0.0361 (1500/41506). AF 95% confidence interval is 0.0346. There are 29 homozygotes in GnomAd4. There are 746 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 29 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207352.4. 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
	CYP4V2	NM_207352.4	MANE Select	c.-130delC		5_prime_UTR	Exon 1 of 11	NP_997235.3	Q6ZWL3-1
	FLJ38576	NR_046264.1		n.-204delG		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4V2	ENST00000378802.5	TSL:1 MANE Select	c.-130delC		5_prime_UTR	Exon 1 of 11	ENSP00000368079.4	Q6ZWL3-1
	CYP4V2	ENST00000905174.1		c.-130delC		5_prime_UTR	Exon 1 of 11	ENSP00000575233.1
	CYP4V2	ENST00000905177.1		c.-130delC		5_prime_UTR	Exon 1 of 11	ENSP00000575236.1

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1563 AN: 151852 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.0360

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

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: 0.0000883

Gnomad OTH AF: 0.00911

GnomAD4 exome AF: 0.00102 AC: 732 AN: 717894 Hom.: 10 Cov.: 10 AF XY: 0.000935 AC XY: 323 AN XY: 345284

African (AFR) AF: 0.0386 AC: 589 AN: 15266

American (AMR) AF: 0.00243 AC: 17 AN: 6998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10798

East Asian (EAS) AF: 0.00 AC: 0 AN: 21950

South Asian (SAS) AF: 0.000148 AC: 2 AN: 13530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2170

European-Non Finnish (NFE) AF: 0.0000504 AC: 30 AN: 595564

Other (OTH) AF: 0.00306 AC: 94 AN: 30684

GnomAD4 genome AF: 0.0103 AC: 1572 AN: 151960 Hom.: 29 Cov.: 33 AF XY: 0.0100 AC XY: 746 AN XY: 74286

African (AFR) AF: 0.0361 AC: 1500 AN: 41506

American (AMR) AF: 0.00308 AC: 47 AN: 15272

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67912

Other (OTH) AF: 0.00901 AC: 19 AN: 2108

Alfa AF: 0.000361 Hom.: 0

Bravo AF: 0.0120

Asia WGS AF: 0.00291 AC: 10 AN: 3454

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Bietti crystalline corneoretinal dystrophy (1)
-	-	1	Corneal Dystrophy, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.3
Mutation Taster		=294/6	polymorphism

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: rs200054565; hg19: chr4-187112847;