Variant chr19-15650077-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2

The NM_000896.3(CYP4F3):c.812T>C(p.Ile271Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00217 in 1,614,176 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0016 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0022 ( 6 hom. )

Consequence

CYP4F3
NM_000896.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.95

Variant links:

Genes affected

CYP4F3 (HGNC:2646): (cytochrome P450 family 4 subfamily F member 3) This gene, CYP4F3, 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, CYP4F8, is approximately 18 kb away. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Apr 2019]

CYP4F3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30112195).

BP6

Variant 19-15650077-T-C is Benign according to our data. Variant chr19-15650077-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 773774.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4F3	NM_000896.3 linkuse as main transcript	c.812T>C	p.Ile271Thr	missense_variant	7/13	ENST00000221307.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4F3	ENST00000221307.13 linkuse as main transcript	c.812T>C	p.Ile271Thr	missense_variant	7/13	1	NM_000896.3	A1	Q08477-1

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

243

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00266

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00144

AC:

362

AN:

251490

Hom.:

AF XY:

0.00157

AC XY:

213

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00225

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00203

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00223

AC:

3257

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

1623

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00259

Gnomad4 FIN exome

AF:

0.000374

Gnomad4 NFE exome

AF:

0.00256

Gnomad4 OTH exome

AF:

0.00162

GnomAD4 genome

AF:

0.00160

AC:

243

AN:

152282

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

126

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.00266

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00185

Hom.:

Bravo

AF:

0.00147

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00124

AC:

151

EpiCase

AF:

0.00262

EpiControl

AF:

0.00196

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

.;.;T;.

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

.;.;D;D

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.30

T;T;T;T

MetaSVM

Uncertain

0.75

MutationAssessor

Pathogenic

4.2

H;H;H;H

MutationTaster

Benign

0.93

D;D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-4.5

.;.;D;.

REVEL

Pathogenic

0.67

Sift

Pathogenic

0.0

.;.;D;.

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

0.99

.;.;D;.

Vest4

0.74

MVP

0.77

MPC

0.29

ClinPred

0.12

GERP RS

4.0

Varity_R

0.81

gMVP

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over