rs1058174

Positions:

• chr22-42140252-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000435101.2(CYP2D7):​n.643C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,452,990 control chromosomes in the GnomAD database, including 19,738 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 0.12 (1609 hom., cov: 28)
  • Exomes 𝑓: 0.15 (18129 hom.)
• Consequence: CYP2D7 ENST00000435101.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2D7	NR_002570.6	n.1540C>T		non_coding_transcript_exon_variant	9/9
CYP2D7	NR_145674.3	n.1597C>T		non_coding_transcript_exon_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2D7	ENST00000435101.2	n.643C>T		non_coding_transcript_exon_variant	5/5	1
CYP2D7	ENST00000358097.8	c.*28C>T		3_prime_UTR_variant	9/9	1		A2
CYP2D7	ENST00000433992.2	c.*28C>T		3_prime_UTR_variant	9/9	1		P5
CYP2D7	ENST00000651010.1	n.3496C>T		non_coding_transcript_exon_variant	9/9

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18431 AN: 151224 Hom.: 1609 Cov.: 28

Gnomad AFR AF: 0.0365

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.0976

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00329

Gnomad SAS AF: 0.0840

Gnomad FIN AF: 0.0936

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.122

GnomAD3 exomes AF: 0.111 AC: 18536 AN: 166730 Hom.: 1375 AF XY: 0.112 AC XY: 10062 AN XY: 89528

Gnomad AFR exome AF: 0.0300

Gnomad AMR exome AF: 0.0663

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.000972

Gnomad SAS exome AF: 0.0736

Gnomad FIN exome AF: 0.0892

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.127

GnomAD4 exome AF: 0.155 AC: 201211 AN: 1301648 Hom.: 18129 Cov.: 26 AF XY: 0.153 AC XY: 98318 AN XY: 642220

Gnomad4 AFR exome AF: 0.0287

Gnomad4 AMR exome AF: 0.0690

Gnomad4 ASJ exome AF: 0.179

Gnomad4 EAS exome AF: 0.000749

Gnomad4 SAS exome AF: 0.0837

Gnomad4 FIN exome AF: 0.0984

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.122 AC: 18424 AN: 151342 Hom.: 1609 Cov.: 28 AF XY: 0.115 AC XY: 8518 AN XY: 73960

Gnomad4 AFR AF: 0.0364

Gnomad4 AMR AF: 0.0976

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.00310

Gnomad4 SAS AF: 0.0833

Gnomad4 FIN AF: 0.0936

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.120

Alfa AF: 0.148 Hom.: 389

Bravo AF: 0.118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.30
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs1058174; hg19: chr22-42536263; COSMIC: COSV63852227; COSMIC: COSV63852227;