rs2241819

Variant names:

• chr4-186191672-A-G
• rs2241819
• NM_207352.4:c.-152A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-186191672-A-G
• chr4-186191672-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_207352.4(CYP4V2):​c.-152A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 662,098 control chromosomes in the GnomAD database, including 50,132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12206 hom., cov: 35)
  • Exomes 𝑓: 0.38 (37926 hom.)
• Consequence: CYP4V2 NM_207352.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.29
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 4-186191672-A-G is Benign according to our data. Variant chr4-186191672-A-G is described in ClinVar as Benign. ClinVar VariationId is 348291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 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.-152A>G		5_prime_UTR	Exon 1 of 11	NP_997235.3	Q6ZWL3-1
	FLJ38576	NR_046264.1		n.-182T>C		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.-152A>G		5_prime_UTR	Exon 1 of 11	ENSP00000368079.4	Q6ZWL3-1
	CYP4V2	ENST00000905174.1		c.-152A>G		5_prime_UTR	Exon 1 of 11	ENSP00000575233.1
	CYP4V2	ENST00000905177.1		c.-152A>G		5_prime_UTR	Exon 1 of 11	ENSP00000575236.1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60683 AN: 151616 Hom.: 12201 Cov.: 35

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.406

GnomAD4 exome AF: 0.381 AC: 194549 AN: 510372 Hom.: 37926 Cov.: 7 AF XY: 0.381 AC XY: 95076 AN XY: 249628

African (AFR) AF: 0.393 AC: 4357 AN: 11082

American (AMR) AF: 0.435 AC: 2791 AN: 6410

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 3013 AN: 9068

East Asian (EAS) AF: 0.456 AC: 9119 AN: 20006

South Asian (SAS) AF: 0.421 AC: 3651 AN: 8682

European-Finnish (FIN) AF: 0.392 AC: 7871 AN: 20086

Middle Eastern (MID) AF: 0.411 AC: 691 AN: 1680

European-Non Finnish (NFE) AF: 0.376 AC: 154073 AN: 409976

Other (OTH) AF: 0.384 AC: 8983 AN: 23382

GnomAD4 genome AF: 0.400 AC: 60713 AN: 151726 Hom.: 12206 Cov.: 35 AF XY: 0.401 AC XY: 29766 AN XY: 74170

African (AFR) AF: 0.401 AC: 16620 AN: 41416

American (AMR) AF: 0.442 AC: 6748 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1222 AN: 3468

East Asian (EAS) AF: 0.485 AC: 2473 AN: 5104

South Asian (SAS) AF: 0.460 AC: 2212 AN: 4808

European-Finnish (FIN) AF: 0.391 AC: 4111 AN: 10520

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.382 AC: 25943 AN: 67836

Other (OTH) AF: 0.407 AC: 857 AN: 2108

Alfa AF: 0.378 Hom.: 1366

Bravo AF: 0.403

Asia WGS AF: 0.501 AC: 1731 AN: 3456

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Bietti crystalline corneoretinal dystrophy (1)
-	-	1	Corneal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.4
DANN	Benign	0.83
PhyloP100		-2.3
PromoterAI		0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs2241819; hg19: chr4-187112826;