rs1398007

Variant names:

• chr4-186191678-C-T
• rs1398007
• NM_207352.4:c.-146C>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.-146C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 715,622 control chromosomes in the GnomAD database, including 80,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13809 hom., cov: 33)
  • Exomes 𝑓: 0.48 (66754 hom.)
• Consequence: CYP4V2 NM_207352.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.35
• Publications: 12 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: Illumina, G2P, ClinGen, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet

FLJ38576 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 4-186191678-C-T is Benign according to our data. Variant chr4-186191678-C-T is described in ClinVar as Benign. ClinVar VariationId is 348292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 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.-146C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_997235.3	Q6ZWL3-1
	CYP4V2	NM_207352.4	MANE Select	c.-146C>T		5_prime_UTR	Exon 1 of 11	NP_997235.3	Q6ZWL3-1
	FLJ38576	NR_046264.1		n.-188G>A		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.-146C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000368079.4	Q6ZWL3-1
	CYP4V2	ENST00000378802.5	TSL:1 MANE Select	c.-146C>T		5_prime_UTR	Exon 1 of 11	ENSP00000368079.4	Q6ZWL3-1
	CYP4V2	ENST00000905174.1		c.-146C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000575233.1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 62946 AN: 151580 Hom.: 13807 Cov.: 33

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.431

GnomAD4 exome AF: 0.479 AC: 270197 AN: 563940 Hom.: 66754 Cov.: 8 AF XY: 0.481 AC XY: 131989 AN XY: 274614

African (AFR) AF: 0.291 AC: 3549 AN: 12206

American (AMR) AF: 0.376 AC: 2465 AN: 6558

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 4252 AN: 9502

East Asian (EAS) AF: 0.293 AC: 6028 AN: 20582

South Asian (SAS) AF: 0.402 AC: 3997 AN: 9938

European-Finnish (FIN) AF: 0.465 AC: 9431 AN: 20300

Middle Eastern (MID) AF: 0.415 AC: 749 AN: 1804

European-Non Finnish (NFE) AF: 0.498 AC: 228091 AN: 457730

Other (OTH) AF: 0.460 AC: 11635 AN: 25320

GnomAD4 genome AF: 0.415 AC: 62958 AN: 151682 Hom.: 13809 Cov.: 33 AF XY: 0.409 AC XY: 30349 AN XY: 74124

African (AFR) AF: 0.295 AC: 12231 AN: 41400

American (AMR) AF: 0.384 AC: 5863 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1498 AN: 3466

East Asian (EAS) AF: 0.294 AC: 1496 AN: 5094

South Asian (SAS) AF: 0.382 AC: 1841 AN: 4816

European-Finnish (FIN) AF: 0.450 AC: 4727 AN: 10512

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.501 AC: 33957 AN: 67832

Other (OTH) AF: 0.432 AC: 909 AN: 2102

Alfa AF: 0.459 Hom.: 2047

Bravo AF: 0.402

Asia WGS AF: 0.345 AC: 1194 AN: 3466

ClinVar

ClinVar submissions

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	-0.72
CADD	Benign	0.26
DANN	Benign	0.91
PhyloP100		-4.3
PromoterAI		-0.037	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: rs1398007; hg19: chr4-187112832;