Genetic Variant NM_000774.5:c.22A>G (chr19-41116210-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000774.5(CYP2F1):c.22A>G(p.Ile8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CYP2F1
NM_000774.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.49

Publications

1 publications found

Variant links:

Genes affected

CYP2F1 (HGNC:2632): (cytochrome P450 family 2 subfamily F member 1) 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 and is known to dehydrogenate 3-methylindole, an endogenous toxin derived from the fermentation of tryptophan, as well as xenobiotic substrates such as naphthalene and ethoxycoumarin. This gene is part of a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. [provided by RefSeq, Jul 2008]

CYP2F1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052353084).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000774.5. 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
	CYP2F1	NM_000774.5	MANE Select	c.22A>G	p.Ile8Val	missense	Exon 2 of 10	NP_000765.2
	CYP2F1	NR_135528.2		n.94A>G		non_coding_transcript_exon	Exon 2 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYP2F1	ENST00000331105.7	TSL:1 MANE Select	c.22A>G	p.Ile8Val	missense	Exon 2 of 10	ENSP00000333534.2	P24903-1
CYP2F1	ENST00000532164.2	TSL:1	n.22A>G		non_coding_transcript_exon	Exon 2 of 10	ENSP00000471416.1	P24903-2
CYP2F1	ENST00000903858.1		c.22A>G	p.Ile8Val	missense	Exon 2 of 10	ENSP00000573917.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461712

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727176

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111924

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.20

(source)

DANN

Benign

0.15

DEOGEN2

Benign

0.0022

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.32

M_CAP

Benign

0.012

MetaRNN

Benign

0.052

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-1.5

PrimateAI

Benign

0.27

PROVEAN

Benign

0.33

REVEL

Benign

0.041

Sift

Benign

0.87

Sift4G

Benign

0.84

Polyphen

0.0

Vest4

0.057

MutPred

0.41

Gain of catalytic residue at I8 (P = 0.0618)

MVP

0.40

MPC

0.27

ClinPred

0.047

GERP RS

-1.2

Varity_R

0.033

gMVP

0.063

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over