Genetic Variant CYP2F1:c.335-8C>G (chr19-41120339-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000774.5(CYP2F1):c.335-8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00369 in 1,581,122 control chromosomes in the GnomAD database, including 204 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 98 hom., cov: 30)

Exomes 𝑓: 0.0021 ( 106 hom. )

Consequence

CYP2F1
NM_000774.5 splice_region, intron

Scores

Splicing: ADA: 0.00003523

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.497

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 19-41120339-C-G is Benign according to our data. Variant chr19-41120339-C-G is described in ClinVar as [Benign]. Clinvar id is 771520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2F1	NM_000774.5 link	c.335-8C>G		splice_region_variant, intron_variant	Intron 3 of 9	ENST00000331105.7	NP_000765.2	P24903-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYP2F1	ENST00000331105.7 link	c.335-8C>G	splice_region_variant, intron_variant	Intron 3 of 9	1	NM_000774.5	ENSP00000333534.2	P24903-1
CYP2F1	ENST00000532164.2 link	n.335-8C>G	splice_region_variant, intron_variant	Intron 3 of 9	1		ENSP00000471416.1	P24903-2
CYP2F1	ENST00000526093.5 link	n.225-1618C>G	intron_variant	Intron 2 of 3	4
CYP2F1	ENST00000531409.5 link	n.410-8C>G	splice_region_variant, intron_variant	Intron 3 of 7	2

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2861

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0655

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00616

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0101

GnomAD3 exomes

AF:

0.00538

AC:

1224

AN:

227366

Hom.:

AF XY:

0.00369

AC XY:

456

AN XY:

123496

show subpopulations

Gnomad AFR exome

AF:

0.0690

Gnomad AMR exome

AF:

0.00363

Gnomad ASJ exome

AF:

0.000233

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000152

Gnomad FIN exome

AF:

0.0000473

Gnomad NFE exome

AF:

0.000234

Gnomad OTH exome

AF:

0.00240

GnomAD4 exome

AF:

0.00208

AC:

2965

AN:

1428856

Hom.:

106

Cov.:

AF XY:

0.00177

AC XY:

1255

AN XY:

708726

show subpopulations

Gnomad4 AFR exome

AF:

0.0725

Gnomad4 AMR exome

AF:

0.00385

Gnomad4 ASJ exome

AF:

0.000121

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000195

Gnomad4 FIN exome

AF:

0.0000377

Gnomad4 NFE exome

AF:

0.000154

Gnomad4 OTH exome

AF:

0.00534

GnomAD4 genome

AF:

0.0189

AC:

2876

AN:

152266

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

1337

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0657

Gnomad4 AMR

AF:

0.00615

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00995

Alfa

AF:

0.00640

Hom.:

Bravo

AF:

0.0223

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.3

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000035

dbscSNV1_RF

Benign

0.054

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