chr22-42130578-C-A

Variant names:

• chr22-42130578-C-A
• rs1080995
• NM_000106.6:c.180+34G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000645361.2(CYP2D6):​c.180+34G>T 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 0.0 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP2D6 ENST00000645361.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 16 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=0.105).

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+34G>T		intron	N/A	NP_000097.3
	CYP2D6	NM_001025161.3		c.180+34G>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+34G>T		intron	N/A	ENSP00000496150.1
	CYP2D6	ENST00000359033.4	TSL:1	c.180+34G>T		intron	N/A	ENSP00000351927.4
	CYP2D6	ENST00000360124.10	TSL:1	n.180+34G>T		intron	N/A	ENSP00000353241.6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 103100 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: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 972164 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 486762

African (AFR) AF: 0.00 AC: 0 AN: 22286

American (AMR) AF: 0.00 AC: 0 AN: 32302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18658

East Asian (EAS) AF: 0.00 AC: 0 AN: 35868

South Asian (SAS) AF: 0.00 AC: 0 AN: 60226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3482

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 715968

Other (OTH) AF: 0.00 AC: 0 AN: 42246

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 103100 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 49684

African (AFR) AF: 0.00 AC: 0 AN: 27478

American (AMR) AF: 0.00 AC: 0 AN: 10438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2298

East Asian (EAS) AF: 0.00 AC: 0 AN: 4490

South Asian (SAS) AF: 0.00 AC: 0 AN: 2920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 180

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 46840

Other (OTH) AF: 0.00 AC: 0 AN: 1354

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.10
PhyloP100		-1.5
PromoterAI		-0.0013	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1080995;