Variant rs1081003 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_000106.6(CYP2D6):c.336C>T(p.Phe112=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 1,609,512 control chromosomes in the GnomAD database, including 8,957 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

Frequency

Genomes: 𝑓 0.063 ( 1286 hom., cov: 32)

Exomes 𝑓: 0.044 ( 7671 hom. )

Consequence

CYP2D6
NM_000106.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.98

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]

CYP2D6 links:

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

NDUFA6-DT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 22-42129754-G-A is Benign according to our data. Variant chr22-42129754-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.98 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2D6	NM_000106.6 linkuse as main transcript	c.336C>T	p.Phe112=	synonymous_variant	2/9	ENST00000645361.2	NP_000097.3
CYP2D6	NM_001025161.3 linkuse as main transcript	c.336C>T	p.Phe112=	synonymous_variant	2/8		NP_001020332.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2D6	ENST00000645361.2 linkuse as main transcript	c.336C>T	p.Phe112=	synonymous_variant	2/9		NM_000106.6	ENSP00000496150	P1	P10635-1
NDUFA6-DT	ENST00000439129.5 linkuse as main transcript	n.1718+4347G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0634

AC:

9592

AN:

151270

Hom.:

1288

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0846

Gnomad AMI

AF:

0.0455

Gnomad AMR

AF:

0.0502

Gnomad ASJ

AF:

0.0559

Gnomad EAS

AF:

0.537

Gnomad SAS

AF:

0.0780

Gnomad FIN

AF:

0.0163

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0254

Gnomad OTH

AF:

0.0491

GnomAD3 exomes

AF:

0.0788

AC:

19325

AN:

245240

Hom.:

3643

AF XY:

0.0743

AC XY:

9940

AN XY:

133780

show subpopulations

Gnomad AFR exome

AF:

0.0852

Gnomad AMR exome

AF:

0.0504

Gnomad ASJ exome

AF:

0.0590

Gnomad EAS exome

AF:

0.572

Gnomad SAS exome

AF:

0.0642

Gnomad FIN exome

AF:

0.0178

Gnomad NFE exome

AF:

0.0251

Gnomad OTH exome

AF:

0.0570

GnomAD4 exome

AF:

0.0438

AC:

63897

AN:

1458130

Hom.:

7671

Cov.:

AF XY:

0.0441

AC XY:

32023

AN XY:

725446

show subpopulations

Gnomad4 AFR exome

AF:

0.0862

Gnomad4 AMR exome

AF:

0.0514

Gnomad4 ASJ exome

AF:

0.0576

Gnomad4 EAS exome

AF:

0.479

Gnomad4 SAS exome

AF:

0.0646

Gnomad4 FIN exome

AF:

0.0188

Gnomad4 NFE exome

AF:

0.0249

Gnomad4 OTH exome

AF:

0.0644

GnomAD4 genome

AF:

0.0633

AC:

9585

AN:

151382

Hom.:

1286

Cov.:

AF XY:

0.0657

AC XY:

4862

AN XY:

73976

show subpopulations

Gnomad4 AFR

AF:

0.0844

Gnomad4 AMR

AF:

0.0501

Gnomad4 ASJ

AF:

0.0559

Gnomad4 EAS

AF:

0.537

Gnomad4 SAS

AF:

0.0772

Gnomad4 FIN

AF:

0.0163

Gnomad4 NFE

AF:

0.0254

Gnomad4 OTH

AF:

0.0486

Alfa

AF:

0.0359

Hom.:

132

Bravo

AF:

0.0697

Asia WGS

AF:

0.231

AC:

798

AN:

3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.2

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over