rs1800754

chr22-42141587-G-Achr22-42141587-G-Cchr22-42141587-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000433992.2(CYP2D7):c.933C>T(p.Leu311=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2D7	NR_002570.6	n.952C>T		non_coding_transcript_exon_variant	6/9
CYP2D7	NR_145674.3	n.952C>T		non_coding_transcript_exon_variant	6/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2D7	ENST00000433992.2	c.933C>T	p.Leu311=	synonymous_variant	6/9	1		P5

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

Gnomad4 AFR exome AF: 0.331

Gnomad4 AMR exome AF: 0.390

Gnomad4 ASJ exome AF: 0.623

Gnomad4 EAS exome AF: 0.608

Gnomad4 SAS exome AF: 0.524

Gnomad4 FIN exome AF: 0.495

Gnomad4 NFE exome AF: 0.518

Gnomad4 OTH exome AF: 0.523

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

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.666

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.494

Alfa AF: 0.531 Hom.: 4044

Bravo AF: 0.475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_noAF	Benign	-0.76
Cadd	Benign	0.38
LIST_S2	Benign	0.81	T;T
MetaRNN	Benign	0.014	T;T
Vest4		0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1800754; hg19: chr22-42537597;