22-42130571-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.66
Variant links:
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)

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ACMG classification

Classification made for transcript

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
CYP2D6NM_000106.6 linkc.180+41C>A intron_variant Intron 1 of 8 ENST00000645361.2 NP_000097.3 P10635-1C1ID52Q5Y7H2
CYP2D6NM_001025161.3 linkc.180+41C>A intron_variant Intron 1 of 7 NP_001020332.2 P10635-2Q5Y7H2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CYP2D6ENST00000645361.2 linkc.180+41C>A intron_variant Intron 1 of 8 NM_000106.6 ENSP00000496150.1 P10635-1
CYP2D6ENST00000359033.4 linkc.180+41C>A intron_variant Intron 1 of 7 1 ENSP00000351927.4 P10635-2
CYP2D6ENST00000488442.1 linkn.243C>A non_coding_transcript_exon_variant Exon 1 of 8 5
NDUFA6-DTENST00000439129.5 linkn.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
show subpopulations
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
show subpopulations
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1080996; hg19: -; API