rs1080997

Variant names:

• chr22-42130569-G-A
• rs1080997
• NM_000106.6:c.180+43C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-42130569-G-A
• chr22-42130569-G-C
• chr22-42130569-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000645361.2(CYP2D6):​c.180+43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000425 in 1,177,654 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000095 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: CYP2D6 ENST00000645361.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 7 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (Cadd=1.282).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000645361.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2D6	NM_000106.6	MANE Select	c.180+43C>T		intron	N/A	NP_000097.3
	CYP2D6	NM_001025161.3		c.180+43C>T		intron	N/A	NP_001020332.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2D6	ENST00000645361.2	MANE Select	c.180+43C>T		intron	N/A	ENSP00000496150.1
	CYP2D6	ENST00000359033.4	TSL:1	c.180+43C>T		intron	N/A	ENSP00000351927.4
	CYP2D6	ENST00000360124.10	TSL:1	n.180+43C>T		intron	N/A	ENSP00000353241.6

Frequencies

GnomAD3 genomes AF: 0.00000951 AC: 1 AN: 105182 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000726

GnomAD4 exome AF: 0.00000373 AC: 4 AN: 1072472 Hom.: 0 Cov.: 27 AF XY: 0.00000558 AC XY: 3 AN XY: 537952

African (AFR) AF: 0.00 AC: 0 AN: 24292

American (AMR) AF: 0.00 AC: 0 AN: 35262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20754

East Asian (EAS) AF: 0.00 AC: 0 AN: 36418

South Asian (SAS) AF: 0.0000444 AC: 3 AN: 67532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3796

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 795234

Other (OTH) AF: 0.0000217 AC: 1 AN: 45994

GnomAD4 genome AF: 0.00000951 AC: 1 AN: 105182 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 50760

African (AFR) AF: 0.00 AC: 0 AN: 27768

American (AMR) AF: 0.00 AC: 0 AN: 10706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2344

East Asian (EAS) AF: 0.00 AC: 0 AN: 4558

South Asian (SAS) AF: 0.00 AC: 0 AN: 2914

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 182

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 48044

Other (OTH) AF: 0.000726 AC: 1 AN: 1378

Alfa AF: 0.00 Hom.: 980

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	1.3
PhyloP100		0.0010
PromoterAI		0.0074	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1080997;