22-42130578-C-G

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+34G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 969,088 control chromosomes in the GnomAD database, including 28,570 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.066 (754 hom., cov: 23)
  • Exomes 𝑓: 0.11 (27816 hom.)
• Consequence: CYP2D6 NM_000106.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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]

NDUFA6-DT (HGNC:45273): (NDUFA6 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=0.121).
• BP6: Variant 22-42130578-C-G is Benign according to our data. Variant chr22-42130578-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2D6	NM_000106.6	c.180+34G>C		intron_variant		ENST00000645361.2
CYP2D6	NM_001025161.3	c.180+34G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2D6	ENST00000645361.2	c.180+34G>C		intron_variant			NM_000106.6	P1
NDUFA6-DT	ENST00000439129.5	n.1718+5171C>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0655 AC: 6056 AN: 92438 Hom.: 751 Cov.: 23

Gnomad AFR AF: 0.0653

Gnomad AMI AF: 0.0369

Gnomad AMR AF: 0.0684

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.0171

Gnomad SAS AF: 0.0658

Gnomad FIN AF: 0.0743

Gnomad MID AF: 0.200

Gnomad NFE AF: 0.0657

Gnomad OTH AF: 0.0736

GnomAD4 exome AF: 0.113 AC: 98999 AN: 876594 Hom.: 27816 Cov.: 29 AF XY: 0.121 AC XY: 52718 AN XY: 436838

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.134

Gnomad4 ASJ exome AF: 0.251

Gnomad4 EAS exome AF: 0.0544

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.259

Gnomad4 NFE exome AF: 0.0910

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.0655 AC: 6060 AN: 92494 Hom.: 754 Cov.: 23 AF XY: 0.0642 AC XY: 2871 AN XY: 44746

Gnomad4 AFR AF: 0.0653

Gnomad4 AMR AF: 0.0687

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.0169

Gnomad4 SAS AF: 0.0667

Gnomad4 FIN AF: 0.0743

Gnomad4 NFE AF: 0.0657

Gnomad4 OTH AF: 0.0733

Alfa AF: 0.314 Hom.: 1672

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Cadd	Benign	0.12

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1080995; hg19: -;