22-42130569-G-C

Position:

• chr22-42130569-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000106.6(CYP2D6):​c.180+43C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 954,444 control chromosomes in the GnomAD database, including 23,313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.044 (314 hom., cov: 23)
  • Exomes 𝑓: 0.072 (23313 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP2D6 NM_000106.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

Genes affected

CYP2D6 (HGNC:2625): (cytochrome P450 family 2 subfamily D member 6) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is known to metabolize as many as 25% of commonly prescribed drugs. Its substrates include antidepressants, antipsychotics, analgesics and antitussives, beta adrenergic blocking agents, antiarrythmics and antiemetics. The gene is highly polymorphic in the human population; certain alleles result in the poor metabolizer phenotype, characterized by a decreased ability to metabolize the enzyme's substrates. Some individuals with the poor metabolizer phenotype have no functional protein since they carry 2 null alleles whereas in other individuals the gene is absent. This gene can vary in copy number and individuals with the ultrarapid metabolizer phenotype can have 3 or more active copies of the gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

CYP2D6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=1.032).
• BP6: Variant 22-42130569-G-C is Benign according to our data. Variant chr22-42130569-G-C is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2D6	NM_000106.6	c.180+43C>G		intron_variant		ENST00000645361.2	NP_000097.3
CYP2D6	NM_001025161.3	c.180+43C>G		intron_variant			NP_001020332.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2D6	ENST00000645361.2	c.180+43C>G		intron_variant			NM_000106.6	ENSP00000496150.1
CYP2D6	ENST00000359033.4	c.180+43C>G		intron_variant		1		ENSP00000351927.4
CYP2D6	ENST00000488442.1	n.245C>G		non_coding_transcript_exon_variant	1/8	5
NDUFA6-DT	ENST00000439129.5	n.1718+5162G>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 4038 AN: 91918 Hom.: 310 Cov.: 23 FAILED QC

Gnomad AFR AF: 0.0470

Gnomad AMI AF: 0.0302

Gnomad AMR AF: 0.0491

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.0101

Gnomad SAS AF: 0.0399

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0413

Gnomad OTH AF: 0.0547

GnomAD4 exome AF: 0.0725 AC: 69167 AN: 954444 Hom.: 23313 Cov.: 27 AF XY: 0.0772 AC XY: 36688 AN XY: 474980

Gnomad4 AFR exome AF: 0.0942

Gnomad4 AMR exome AF: 0.0877

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.0397

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.0564

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0439 AC: 4040 AN: 91968 Hom.: 314 Cov.: 23 AF XY: 0.0430 AC XY: 1918 AN XY: 44602

Gnomad4 AFR AF: 0.0470

Gnomad4 AMR AF: 0.0493

Gnomad4 ASJ AF: 0.0836

Gnomad4 EAS AF: 0.00989

Gnomad4 SAS AF: 0.0416

Gnomad4 FIN AF: 0.0524

Gnomad4 NFE AF: 0.0413

Gnomad4 OTH AF: 0.0546

Alfa AF: 0.193 Hom.: 980

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1080997; hg19: -;