22-42140252-G-A

Variant names:

• chr22-42140252-G-A
• rs1058174
• ENST00000435101.2:n.643C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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 -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 rank	MANE	Protein	UniProt
CYP2D7	NR_002570.6	n.1540C>T		non_coding_transcript_exon_variant	Exon 9 of 9
CYP2D7	NR_145674.3	n.1597C>T		non_coding_transcript_exon_variant	Exon 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2D7	ENST00000435101.2	n.643C>T		non_coding_transcript_exon_variant	Exon 5 of 5	1
CYP2D7	ENST00000433992.2	c.*28C>T		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000439604.1
CYP2D7	ENST00000358097.8	c.*28C>T		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000445124.1
CYP2D7	ENST00000651010.1	n.3496C>T		non_coding_transcript_exon_variant	Exon 9 of 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

GnomAD2 exomes AF: 0.111 AC: 18536 AN: 166730 AF XY: 0.112

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 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

African (AFR) AF: 0.0287 AC: 839 AN: 29270

American (AMR) AF: 0.0690 AC: 2086 AN: 30244

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 3581 AN: 20020

East Asian (EAS) AF: 0.000749 AC: 29 AN: 38700

South Asian (SAS) AF: 0.0837 AC: 5970 AN: 71324

European-Finnish (FIN) AF: 0.0984 AC: 4865 AN: 49430

Middle Eastern (MID) AF: 0.102 AC: 467 AN: 4590

European-Non Finnish (NFE) AF: 0.175 AC: 176151 AN: 1004092

Other (OTH) AF: 0.134 AC: 7223 AN: 53978

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

African (AFR) AF: 0.0364 AC: 1504 AN: 41328

American (AMR) AF: 0.0976 AC: 1485 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 649 AN: 3444

East Asian (EAS) AF: 0.00310 AC: 16 AN: 5160

South Asian (SAS) AF: 0.0833 AC: 398 AN: 4780

European-Finnish (FIN) AF: 0.0936 AC: 985 AN: 10518

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12883 AN: 67602

Other (OTH) AF: 0.120 AC: 251 AN: 2094

Alfa AF: 0.145 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
PhyloP100		-1.6

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