rs13146272

Variant names:

• chr4-186199057-C-A
• rs13146272
• NM_207352.4:c.775C>A
• CYP4V2 p.Gln259Lys

Your query was ambiguous. Multiple possible variants found:

• chr4-186199057-C-A
• chr4-186199057-C-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 1P and 20B. PP2 BP4_Strong BP6_Very_Strong BA1

The NM_207352.4(CYP4V2):​c.775C>A​(p.Gln259Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 1,612,180 control chromosomes in the GnomAD database, including 310,979 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (28214 hom., cov: 32)
  • Exomes 𝑓: 0.62 (282765 hom.)
• Consequence: CYP4V2 NM_207352.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 2.23
• Publications: 105 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: Orphanet, Laboratory for Molecular Medicine, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Illumina

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 24 curated pathogenic missense variants (we use a threshold of 10). The gene has 7 curated benign missense variants. Gene score misZ: -0.12103 (below the threshold of 3.09). Trascript score misZ: -0.14191 (below the threshold of 3.09). GenCC associations: The gene is linked to Bietti crystalline corneoretinal dystrophy.
• BP4: Computational evidence support a benign effect (MetaRNN=1.9090473E-6).
• BP6: Variant 4-186199057-C-A is Benign according to our data. Variant chr4-186199057-C-A is described in ClinVar as Benign. ClinVar VariationId is 263297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

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.775C>A	p.Gln259Lys	missense	Exon 6 of 11	NP_997235.3	Q6ZWL3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4V2	ENST00000378802.5	TSL:1 MANE Select	c.775C>A	p.Gln259Lys	missense	Exon 6 of 11	ENSP00000368079.4	Q6ZWL3-1
	CYP4V2	ENST00000507209.5	TSL:1	n.1616C>A		non_coding_transcript_exon	Exon 2 of 6
	CYP4V2	ENST00000905173.1		c.775C>A	p.Gln259Lys	missense	Exon 6 of 12	ENSP00000575232.1

Frequencies

GnomAD3 genomes AF: 0.606 AC: 92014 AN: 151902 Hom.: 28197 Cov.: 32

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.593

GnomAD2 exomes AF: 0.573 AC: 144116 AN: 251344 AF XY: 0.583

Gnomad AFR exome AF: 0.616

Gnomad AMR exome AF: 0.373

Gnomad ASJ exome AF: 0.517

Gnomad EAS exome AF: 0.393

Gnomad FIN exome AF: 0.664

Gnomad NFE exome AF: 0.637

Gnomad OTH exome AF: 0.567

GnomAD4 exome AF: 0.618 AC: 902697 AN: 1460160 Hom.: 282765 Cov.: 49 AF XY: 0.619 AC XY: 449627 AN XY: 726452

African (AFR) AF: 0.603 AC: 20178 AN: 33450

American (AMR) AF: 0.383 AC: 17141 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 13610 AN: 26124

East Asian (EAS) AF: 0.388 AC: 15391 AN: 39672

South Asian (SAS) AF: 0.604 AC: 52085 AN: 86216

European-Finnish (FIN) AF: 0.666 AC: 35556 AN: 53388

Middle Eastern (MID) AF: 0.545 AC: 3142 AN: 5766

European-Non Finnish (NFE) AF: 0.639 AC: 709347 AN: 1110508

Other (OTH) AF: 0.601 AC: 36247 AN: 60312

GnomAD4 genome AF: 0.606 AC: 92073 AN: 152020 Hom.: 28214 Cov.: 32 AF XY: 0.605 AC XY: 44982 AN XY: 74316

African (AFR) AF: 0.610 AC: 25281 AN: 41462

American (AMR) AF: 0.489 AC: 7465 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1768 AN: 3468

East Asian (EAS) AF: 0.416 AC: 2144 AN: 5158

South Asian (SAS) AF: 0.606 AC: 2917 AN: 4816

European-Finnish (FIN) AF: 0.662 AC: 6994 AN: 10568

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43475 AN: 67964

Other (OTH) AF: 0.595 AC: 1250 AN: 2102

Alfa AF: 0.614 Hom.: 132282

Bravo AF: 0.584

Asia WGS AF: 0.529 AC: 1842 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Bietti crystalline corneoretinal dystrophy (3)
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Corneal dystrophy (1)
-	-	1	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.0
DANN	Benign	0.27
DEOGEN2	Benign	0.050	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0000019	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.2	N
PhyloP100		2.2
PrimateAI	Benign	0.27	T
PROVEAN	Benign	2.0	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Varity_R		0.13
gMVP		0.41
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs13146272;

hg19: chr4-187120211;

COSMIC: COSV66505019;