rs1055138

Variant names:

• chr4-186191887-C-G
• rs1055138
• NM_207352.4:c.64C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-186191887-C-G
• chr4-186191887-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.64C>G​(p.Leu22Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,587,696 control chromosomes in the GnomAD database, including 186,194 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16288 hom., cov: 34)
  • Exomes 𝑓: 0.48 (169906 hom.)
• Consequence: CYP4V2 NM_207352.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 B:15
• Conservation: PhyloP100: -0.996
• Publications: 45 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

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=3.741501E-5).
• BP6: Variant 4-186191887-C-G is Benign according to our data. Variant chr4-186191887-C-G is described in ClinVar as Benign. ClinVar VariationId is 39267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.501 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.64C>G	p.Leu22Val	missense	Exon 1 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.64C>G	p.Leu22Val	missense	Exon 1 of 11	ENSP00000368079.4	Q6ZWL3-1
	CYP4V2	ENST00000905173.1		c.64C>G	p.Leu22Val	missense	Exon 1 of 12	ENSP00000575232.1
	CYP4V2	ENST00000905174.1		c.64C>G	p.Leu22Val	missense	Exon 1 of 11	ENSP00000575233.1

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69750 AN: 151928 Hom.: 16272 Cov.: 34

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.460

GnomAD2 exomes AF: 0.444 AC: 89568 AN: 201924 AF XY: 0.447

Gnomad AFR exome AF: 0.424

Gnomad AMR exome AF: 0.387

Gnomad ASJ exome AF: 0.466

Gnomad EAS exome AF: 0.272

Gnomad FIN exome AF: 0.454

Gnomad NFE exome AF: 0.505

Gnomad OTH exome AF: 0.467

GnomAD4 exome AF: 0.484 AC: 694802 AN: 1435650 Hom.: 169906 Cov.: 75 AF XY: 0.482 AC XY: 343795 AN XY: 712832

African (AFR) AF: 0.425 AC: 14045 AN: 33024

American (AMR) AF: 0.393 AC: 16606 AN: 42232

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 12040 AN: 25734

East Asian (EAS) AF: 0.284 AC: 10951 AN: 38572

South Asian (SAS) AF: 0.405 AC: 33857 AN: 83504

European-Finnish (FIN) AF: 0.462 AC: 20446 AN: 44278

Middle Eastern (MID) AF: 0.448 AC: 2449 AN: 5464

European-Non Finnish (NFE) AF: 0.504 AC: 556326 AN: 1103380

Other (OTH) AF: 0.472 AC: 28082 AN: 59462

GnomAD4 genome AF: 0.459 AC: 69805 AN: 152046 Hom.: 16288 Cov.: 34 AF XY: 0.453 AC XY: 33718 AN XY: 74360

African (AFR) AF: 0.427 AC: 17740 AN: 41512

American (AMR) AF: 0.423 AC: 6465 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1583 AN: 3470

East Asian (EAS) AF: 0.282 AC: 1449 AN: 5130

South Asian (SAS) AF: 0.398 AC: 1920 AN: 4828

European-Finnish (FIN) AF: 0.460 AC: 4876 AN: 10598

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.506 AC: 34344 AN: 67908

Other (OTH) AF: 0.463 AC: 977 AN: 2110

Alfa AF: 0.489 Hom.: 5601

Bravo AF: 0.453

TwinsUK AF: 0.489 AC: 1815

ALSPAC AF: 0.503 AC: 1940

ESP6500AA AF: 0.413 AC: 1786

ESP6500EA AF: 0.489 AC: 4174

ExAC AF: 0.421 AC: 49477

Asia WGS AF: 0.354 AC: 1229 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
1	-	5	Bietti crystalline corneoretinal dystrophy (6)
-	-	4	not provided (4)
-	-	4	not specified (4)
-	-	1	Corneal dystrophy (1)
-	-	1	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.15
DANN	Benign	0.52
DEOGEN2	Benign	0.050	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	0.000037	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.90	N
PhyloP100		-1.0
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.027
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.014
MPC		0.11
ClinPred		0.0066	T
GERP RS		0.68
PromoterAI		-0.059	Neutral
Varity_R		0.039
gMVP		0.50
Mutation Taster		=93/7	polymorphism (auto)

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: rs1055138; hg19: chr4-187113041; COSMIC: COSV66505124; COSMIC: COSV66505124;