Genetic Variant CYP2D7:p.Leu374Leu (chr22-42141263-G-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The ENST00000433992.2(CYP2D7):c.1120C>T(p.Leu374Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000303 in 1,318,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

CYP2D7
ENST00000433992.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0310

Publications

0 publications found

Variant links:

Genes affected

CYP2D7 (HGNC:2624): (cytochrome P450 family 2 subfamily D member 7 (gene/pseudogene)) This gene is a member of the cytochrome P450 gene superfamily. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This gene is a segregating pseudogene, where some individuals may have an allele that encodes a functional enzyme, while other individuals have an allele encoding a protein that is predicted to be non-functional. In this case, the functional allele is thought to be rare. This locus is part of a cluster of cytochrome P450 genes on chromosome 22. [provided by RefSeq, Jan 2017]

CYP2D7 links:

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new If you want to explore the variant's impact on the transcript ENST00000433992.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP7

Synonymous conserved (PhyloP=0.031 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000433992.2. 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
	CYP2D7	NR_002570.6		n.1082C>T		non_coding_transcript_exon	Exon 7 of 9
	CYP2D7	NR_145674.3		n.1139C>T		non_coding_transcript_exon	Exon 7 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CYP2D7	ENST00000433992.2	TSL:1	c.1120C>T	p.Leu374Leu	synonymous	Exon 7 of 9	ENSP00000439604.1
CYP2D7	ENST00000358097.8	TSL:1	c.1063C>T	p.Leu355Leu	synonymous	Exon 7 of 9	ENSP00000445124.1
CYP2D7	ENST00000435101.2	TSL:1	n.185C>T		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000825

AC:

AN:

242500

AF XY:

0.00000762

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000303

AC:

AN:

1318246

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

660948

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26306

American (AMR)

AF:

0.00

AC:

AN:

43270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24864

East Asian (EAS)

AF:

0.00

AC:

AN:

36448

South Asian (SAS)

AF:

0.0000366

AC:

AN:

82020

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51778

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5306

European-Non Finnish (NFE)

AF:

0.00000101

AC:

AN:

993126

Other (OTH)

AF:

0.00

AC:

AN:

55128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

1.8

(source)

DANN

Benign

0.84

PhyloP100

0.031

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over