rs28371702

Variant names:

• chr22-42129950-A-C
• rs28371702
• NM_000106.6:c.181-41T>G

Your query was ambiguous. Multiple possible variants found:

• chr22-42129950-A-C
• chr22-42129950-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000106.6(CYP2D6):​c.181-41T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (24907 hom., cov: 16)
  • Exomes 𝑓: 0.55 (218680 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP2D6 NM_000106.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000106.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2D6	NM_000106.6	MANE Select	c.181-41T>G		intron	N/A	NP_000097.3
	CYP2D6	NM_001025161.3		c.181-41T>G		intron	N/A	NP_001020332.2	P10635-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2D6	ENST00000645361.2	MANE Select	c.181-41T>G		intron	N/A	ENSP00000496150.1	P10635-1
	CYP2D6	ENST00000359033.4	TSL:1	c.181-41T>G		intron	N/A	ENSP00000351927.4	P10635-2
	CYP2D6	ENST00000360124.10	TSL:1	n.181-41T>G		intron	N/A	ENSP00000353241.6	H7BY38

Frequencies

GnomAD3 genomes AF: 0.605 AC: 78874 AN: 130452 Hom.: 24871 Cov.: 16

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.632

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.590

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.554 AC: 747831 AN: 1348904 Hom.: 218680 Cov.: 32 AF XY: 0.555 AC XY: 369697 AN XY: 666704

African (AFR) AF: 0.750 AC: 23463 AN: 31286

American (AMR) AF: 0.432 AC: 15410 AN: 35658

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 16272 AN: 24804

East Asian (EAS) AF: 0.627 AC: 22879 AN: 36502

South Asian (SAS) AF: 0.542 AC: 42783 AN: 78982

European-Finnish (FIN) AF: 0.504 AC: 18795 AN: 37298

Middle Eastern (MID) AF: 0.597 AC: 2457 AN: 4116

European-Non Finnish (NFE) AF: 0.549 AC: 573234 AN: 1043652

Other (OTH) AF: 0.575 AC: 32538 AN: 56606

GnomAD4 genome AF: 0.605 AC: 78946 AN: 130546 Hom.: 24907 Cov.: 16 AF XY: 0.602 AC XY: 37797 AN XY: 62832

African (AFR) AF: 0.738 AC: 24840 AN: 33646

American (AMR) AF: 0.504 AC: 6586 AN: 13074

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2103 AN: 3258

East Asian (EAS) AF: 0.711 AC: 3346 AN: 4706

South Asian (SAS) AF: 0.555 AC: 2019 AN: 3640

European-Finnish (FIN) AF: 0.507 AC: 4408 AN: 8686

Middle Eastern (MID) AF: 0.643 AC: 180 AN: 280

European-Non Finnish (NFE) AF: 0.560 AC: 34018 AN: 60714

Other (OTH) AF: 0.583 AC: 1021 AN: 1750

Alfa AF: 0.535 Hom.: 3213

Bravo AF: 0.612

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
PhyloP100		-2.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs28371702;

hg19: chr22-42525952;