rs2074900

Variant names:

• chr19-15886010-G-A
• rs2074900
• NM_001082.5:c.1029C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001082.5(CYP4F2):​c.1029C>T​(p.His343His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,613,564 control chromosomes in the GnomAD database, including 75,671 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.27 (5765 hom., cov: 30)
  • Exomes 𝑓: 0.31 (69906 hom.)
• Consequence: CYP4F2 NM_001082.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.08

Genes affected

CYP4F2 (HGNC:2645): (cytochrome P450 family 4 subfamily F member 2) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum. The enzyme starts the process of inactivating and degrading leukotriene B4, a potent mediator of inflammation. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F11, is approximately 16 kb away. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.015).
• BP6: Variant 19-15886010-G-A is Benign according to our data. Variant chr19-15886010-G-A is described in ClinVar as [Benign]. Clinvar id is 3056285.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4F2	NM_001082.5	c.1029C>T	p.His343His	synonymous_variant	Exon 9 of 13	ENST00000221700.11	NP_001073.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F2	ENST00000221700.11	c.1029C>T	p.His343His	synonymous_variant	Exon 9 of 13	1	NM_001082.5	ENSP00000221700.3

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40703 AN: 151844 Hom.: 5769 Cov.: 30

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.259

GnomAD2 exomes AF: 0.283 AC: 70998 AN: 251290 AF XY: 0.284

Gnomad AFR exome AF: 0.182

Gnomad AMR exome AF: 0.251

Gnomad ASJ exome AF: 0.253

Gnomad EAS exome AF: 0.245

Gnomad FIN exome AF: 0.299

Gnomad NFE exome AF: 0.318

Gnomad OTH exome AF: 0.276

GnomAD4 exome AF: 0.306 AC: 446849 AN: 1461602 Hom.: 69906 Cov.: 40 AF XY: 0.304 AC XY: 221366 AN XY: 727096

Gnomad4 AFR exome AF: 0.183 AC: 6125 AN: 33478

Gnomad4 AMR exome AF: 0.255 AC: 11408 AN: 44698

Gnomad4 ASJ exome AF: 0.250 AC: 6532 AN: 26128

Gnomad4 EAS exome AF: 0.205 AC: 8142 AN: 39680

Gnomad4 SAS exome AF: 0.262 AC: 22621 AN: 86228

Gnomad4 FIN exome AF: 0.306 AC: 16352 AN: 53398

Gnomad4 NFE exome AF: 0.321 AC: 356790 AN: 1111854

Gnomad4 Remaining exome AF: 0.292 AC: 17642 AN: 60380

GnomAD4 genome AF: 0.268 AC: 40693 AN: 151962 Hom.: 5765 Cov.: 30 AF XY: 0.265 AC XY: 19659 AN XY: 74262

Gnomad4 AFR AF: 0.185 AC: 0.185335 AN: 0.185335

Gnomad4 AMR AF: 0.261 AC: 0.261462 AN: 0.261462

Gnomad4 ASJ AF: 0.253 AC: 0.253026 AN: 0.253026

Gnomad4 EAS AF: 0.232 AC: 0.231769 AN: 0.231769

Gnomad4 SAS AF: 0.264 AC: 0.264143 AN: 0.264143

Gnomad4 FIN AF: 0.295 AC: 0.294954 AN: 0.294954

Gnomad4 NFE AF: 0.319 AC: 0.319434 AN: 0.319434

Gnomad4 OTH AF: 0.256 AC: 0.256398 AN: 0.256398

Alfa AF: 0.290 Hom.: 2860

Bravo AF: 0.259

Asia WGS AF: 0.226 AC: 789 AN: 3478

EpiCase AF: 0.301

EpiControl AF: 0.298

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CYP4F2-related disorder Benign:1

Oct 18, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.8
DANN	Uncertain	0.99
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

Publications

LitVar

Other links and lift over

dbSNP: rs2074900; hg19: chr19-15996820; COSMIC: COSV50000437;