22-42130571-G-T

Variant names:

• chr22-42130571-G-T
• rs1080996
• NM_000106.6:c.180+41C>A

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+41C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0795 in 924,438 control chromosomes in the GnomAD database, including 24,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.047 (378 hom., cov: 23)
  • Exomes 𝑓: 0.080 (24431 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP2D6 NM_000106.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.66

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=0.132).
• BP6: Variant 22-42130571-G-T is Benign according to our data. Variant chr22-42130571-G-T is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2D6	NM_000106.6	c.180+41C>A		intron_variant	Intron 1 of 8	ENST00000645361.2	NP_000097.3
CYP2D6	NM_001025161.3	c.180+41C>A		intron_variant	Intron 1 of 7		NP_001020332.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2D6	ENST00000645361.2	c.180+41C>A		intron_variant	Intron 1 of 8		NM_000106.6	ENSP00000496150.1
CYP2D6	ENST00000359033.4	c.180+41C>A		intron_variant	Intron 1 of 7	1		ENSP00000351927.4
CYP2D6	ENST00000488442.1	n.243C>A		non_coding_transcript_exon_variant	Exon 1 of 8	5
NDUFA6-DT	ENST00000439129.5	n.1718+5164G>T		intron_variant	Intron 5 of 6	5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 4338 AN: 91778 Hom.: 372 Cov.: 23 FAILED QC

Gnomad AFR AF: 0.0492

Gnomad AMI AF: 0.0347

Gnomad AMR AF: 0.0526

Gnomad ASJ AF: 0.0937

Gnomad EAS AF: 0.0115

Gnomad SAS AF: 0.0471

Gnomad FIN AF: 0.0571

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.0448

Gnomad OTH AF: 0.0543

GnomAD4 exome AF: 0.0795 AC: 73500 AN: 924438 Hom.: 24431 Cov.: 27 AF XY: 0.0845 AC XY: 38925 AN XY: 460716

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.0927

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.0434

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.0625

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0473 AC: 4345 AN: 91836 Hom.: 378 Cov.: 23 AF XY: 0.0465 AC XY: 2070 AN XY: 44524

Gnomad4 AFR AF: 0.0494

Gnomad4 AMR AF: 0.0529

Gnomad4 ASJ AF: 0.0937

Gnomad4 EAS AF: 0.0113

Gnomad4 SAS AF: 0.0484

Gnomad4 FIN AF: 0.0571

Gnomad4 NFE AF: 0.0448

Gnomad4 OTH AF: 0.0543

Alfa AF: 0.217 Hom.: 980

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.13

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1080996; hg19: -;