rs267608289
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000106.6(CYP2D6):c.352+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,609,158 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).
Frequency
Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00018 ( 8 hom. )
Consequence
CYP2D6
NM_000106.6 splice_region, intron
NM_000106.6 splice_region, intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.592
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
?
Variant 22-42129731-T-C is Benign according to our data. Variant chr22-42129731-T-C is described in Lovd as [Benign].
BS2
?
High AC in GnomAd at 23 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP2D6 | NM_000106.6 | c.352+7A>G | splice_region_variant, intron_variant | ENST00000645361.2 | |||
CYP2D6 | NM_001025161.3 | c.352+7A>G | splice_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP2D6 | ENST00000645361.2 | c.352+7A>G | splice_region_variant, intron_variant | NM_000106.6 | P1 | ||||
NDUFA6-DT | ENST00000439129.5 | n.1718+4324T>C | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000152 AC: 23AN: 151444Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000200 AC: 49AN: 245570Hom.: 1 AF XY: 0.000231 AC XY: 31AN XY: 133954
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GnomAD4 exome AF: 0.000178 AC: 259AN: 1457714Hom.: 8 Cov.: 32 AF XY: 0.000168 AC XY: 122AN XY: 725264
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GnomAD4 genome ? AF: 0.000152 AC: 23AN: 151444Hom.: 0 Cov.: 32 AF XY: 0.000149 AC XY: 11AN XY: 73964
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Not reported inComputational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at