rs3833221

Variant names:

• chr19-41116202-G-GC
• rs3833221
• NM_000774.5:c.15dupC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000774.5(CYP2F1):​c.15dupC​(p.Thr6HisfsTer22) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,613,132 control chromosomes in the GnomAD database, including 36,556 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5591 hom., cov: 22)
  • Exomes 𝑓: 0.20 (30965 hom.)
• Consequence: CYP2F1 NM_000774.5 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0400
• Publications: 23 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 19-41116202-G-GC is Benign according to our data. Variant chr19-41116202-G-GC is described in ClinVar as Benign. ClinVar VariationId is 402583.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2F1	NM_000774.5	c.15dupC	p.Thr6HisfsTer22	frameshift_variant	Exon 2 of 10	ENST00000331105.7	NP_000765.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2F1	ENST00000331105.7	c.15dupC	p.Thr6HisfsTer22	frameshift_variant	Exon 2 of 10	1	NM_000774.5	ENSP00000333534.2
CYP2F1	ENST00000532164.2	n.15dupC		non_coding_transcript_exon_variant	Exon 2 of 10	1		ENSP00000471416.1
CYP2F1	ENST00000531409.5	n.90dupC		non_coding_transcript_exon_variant	Exon 2 of 8	2
CYP2F1	ENST00000526093.5	n.62-252dupC		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38741 AN: 151644 Hom.: 5576 Cov.: 22

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.231

GnomAD2 exomes AF: 0.208 AC: 52137 AN: 250814 AF XY: 0.208

Gnomad AFR exome AF: 0.398

Gnomad AMR exome AF: 0.138

Gnomad ASJ exome AF: 0.166

Gnomad EAS exome AF: 0.249

Gnomad FIN exome AF: 0.244

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.191

GnomAD4 exome AF: 0.201 AC: 293358 AN: 1461370 Hom.: 30965 Cov.: 34 AF XY: 0.201 AC XY: 146254 AN XY: 726984

African (AFR) AF: 0.406 AC: 13598 AN: 33468

American (AMR) AF: 0.142 AC: 6348 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 4387 AN: 26098

East Asian (EAS) AF: 0.237 AC: 9427 AN: 39700

South Asian (SAS) AF: 0.225 AC: 19400 AN: 86214

European-Finnish (FIN) AF: 0.238 AC: 12721 AN: 53352

Middle Eastern (MID) AF: 0.194 AC: 1118 AN: 5760

European-Non Finnish (NFE) AF: 0.192 AC: 213601 AN: 1111712

Other (OTH) AF: 0.211 AC: 12758 AN: 60382

GnomAD4 genome AF: 0.256 AC: 38807 AN: 151762 Hom.: 5591 Cov.: 22 AF XY: 0.255 AC XY: 18896 AN XY: 74156

African (AFR) AF: 0.400 AC: 16549 AN: 41322

American (AMR) AF: 0.191 AC: 2920 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 580 AN: 3472

East Asian (EAS) AF: 0.254 AC: 1306 AN: 5140

South Asian (SAS) AF: 0.243 AC: 1170 AN: 4810

European-Finnish (FIN) AF: 0.233 AC: 2445 AN: 10510

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13020 AN: 67942

Other (OTH) AF: 0.233 AC: 490 AN: 2104

Alfa AF: 0.205 Hom.: 2350

Bravo AF: 0.257

Asia WGS AF: 0.311 AC: 1084 AN: 3478

EpiCase AF: 0.180

EpiControl AF: 0.184

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 3199/12518=25.55% -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.040
Mutation Taster		=128/72	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

Other links and lift over

dbSNP: rs3833221; hg19: chr19-41622107; COSMIC: COSV58526583;