rs199930248

Variant names:

• chr19-41116210-A-C
• rs199930248
• NM_000774.5:c.22A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-41116210-A-C
• chr19-41116210-A-G
• chr19-41116210-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000774.5(CYP2F1):​c.22A>C​(p.Ile8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I8V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CYP2F1 NM_000774.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 1 publications found

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]

ACMG classification

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=0.06101668).

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>C	p.Ile8Leu	missense	Exon 2 of 10	NP_000765.2
	CYP2F1	NR_135528.2		n.94A>C		non_coding_transcript_exon	Exon 2 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2F1	ENST00000331105.7	TSL:1 MANE Select	c.22A>C	p.Ile8Leu	missense	Exon 2 of 10	ENSP00000333534.2	P24903-1
	CYP2F1	ENST00000532164.2	TSL:1	n.22A>C		non_coding_transcript_exon	Exon 2 of 10	ENSP00000471416.1	P24903-2
	CYP2F1	ENST00000903858.1		c.22A>C	p.Ile8Leu	missense	Exon 2 of 10	ENSP00000573917.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.16
DANN	Benign	0.48
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.5
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.53		Loss of catalytic residue at L13 (P = 0.0649)
MVP		0.36
MPC		0.32
ClinPred		0.052	T
GERP RS		-1.2
Varity_R		0.062
gMVP		0.084
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs199930248; hg19: chr19-41622115;