22-42141587-G-A

Variant names:

• chr22-42141587-G-A
• rs1800754
• ENST00000433992.2:c.933C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000433992.2(CYP2D7):​c.933C>T​(p.Leu311Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 1,491,678 control chromosomes in the GnomAD database, including 200,307 homozygotes. 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: 𝑓 0.49 (18692 hom., cov: 33)
  • Exomes 𝑓: 0.51 (181615 hom.)
• Consequence: CYP2D7 ENST00000433992.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• Publications: 22 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013934463).
• BP7: Synonymous conserved (PhyloP=1.88 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2D7	NR_002570.6		n.952C>T		non_coding_transcript_exon	Exon 6 of 9
	CYP2D7	NR_145674.3		n.952C>T		non_coding_transcript_exon	Exon 6 of 9

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2D7	ENST00000433992.2	TSL:1	c.933C>T	p.Leu311Leu	synonymous	Exon 6 of 9	ENSP00000439604.1
	CYP2D7	ENST00000358097.8	TSL:1	c.933C>T	p.Leu311Leu	synonymous	Exon 6 of 9	ENSP00000445124.1
	CYP2D7	ENST00000610593.4	TSL:1	n.1018C>T		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73747 AN: 151840 Hom.: 18680 Cov.: 33

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.498

GnomAD4 exome AF: 0.514 AC: 688064 AN: 1339720 Hom.: 181615 Cov.: 30 AF XY: 0.517 AC XY: 347740 AN XY: 672196

African (AFR) AF: 0.331 AC: 10464 AN: 31600

American (AMR) AF: 0.390 AC: 17368 AN: 44536

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 15752 AN: 25276

East Asian (EAS) AF: 0.608 AC: 23667 AN: 38928

South Asian (SAS) AF: 0.524 AC: 43757 AN: 83580

European-Finnish (FIN) AF: 0.495 AC: 26306 AN: 53158

Middle Eastern (MID) AF: 0.525 AC: 2900 AN: 5524

European-Non Finnish (NFE) AF: 0.518 AC: 518500 AN: 1000982

Other (OTH) AF: 0.523 AC: 29350 AN: 56136

GnomAD4 genome AF: 0.486 AC: 73788 AN: 151958 Hom.: 18692 Cov.: 33 AF XY: 0.485 AC XY: 36057 AN XY: 74288

African (AFR) AF: 0.355 AC: 14701 AN: 41464

American (AMR) AF: 0.456 AC: 6973 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2151 AN: 3472

East Asian (EAS) AF: 0.666 AC: 3435 AN: 5156

South Asian (SAS) AF: 0.541 AC: 2604 AN: 4814

European-Finnish (FIN) AF: 0.494 AC: 5229 AN: 10576

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37015 AN: 67888

Other (OTH) AF: 0.494 AC: 1043 AN: 2112

Alfa AF: 0.531 Hom.: 4044

Bravo AF: 0.475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.38
DEOGEN2	Benign	0.099	T
LIST_S2	Benign	0.81	T
MetaRNN	Benign	0.014	T
PhyloP100		1.9
Vest4		0.57

Splicing

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

Other links and lift over

dbSNP: rs1800754; hg19: chr22-42537597;