22-42141261-C-T

Position:

• chr22-42141261-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000433992.2(CYP2D7):​c.1122G>A​(p.Leu374Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 145,170 control chromosomes in the GnomAD database, including 39,928 homozygotes. 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 0.73 (39928 hom., cov: 26)
  • Exomes 𝑓: 0.63 (240515 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP2D7 ENST00000433992.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153

Genes affected

CYP2D7 (HGNC:2624): (cytochrome P450 family 2 subfamily D member 7 (gene/pseudogene)) This gene is a member of the cytochrome P450 gene superfamily. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This gene is a segregating pseudogene, where some individuals may have an allele that encodes a functional enzyme, while other individuals have an allele encoding a protein that is predicted to be non-functional. In this case, the functional allele is thought to be rare. This locus is part of a cluster of cytochrome P450 genes on chromosome 22. [provided by RefSeq, Jan 2017]

CYP2D7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008505195).
• BP7: Synonymous conserved (PhyloP=-0.153 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2D7	NR_002570.6	n.1084G>A		non_coding_transcript_exon_variant	7/9
CYP2D7	NR_145674.3	n.1141G>A		non_coding_transcript_exon_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2D7	ENST00000433992.2	c.1122G>A	p.Leu374Leu	synonymous_variant	7/9	1		ENSP00000439604.1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 105576 AN: 145054 Hom.: 39880 Cov.: 26

Gnomad AFR AF: 0.928

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.693

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.625 AC: 732248 AN: 1170994 Hom.: 240515 Cov.: 27 AF XY: 0.625 AC XY: 368641 AN XY: 590240

Gnomad4 AFR exome AF: 0.930

Gnomad4 AMR exome AF: 0.532

Gnomad4 ASJ exome AF: 0.656

Gnomad4 EAS exome AF: 0.641

Gnomad4 SAS exome AF: 0.556

Gnomad4 FIN exome AF: 0.651

Gnomad4 NFE exome AF: 0.624

Gnomad4 OTH exome AF: 0.642

GnomAD4 genome AF: 0.728 AC: 105666 AN: 145170 Hom.: 39928 Cov.: 26 AF XY: 0.722 AC XY: 51058 AN XY: 70674

Gnomad4 AFR AF: 0.928

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.691

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.667

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.687

Alfa AF: 0.615 Hom.: 2994

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
CADD	Benign	0.33
DEOGEN2	Benign	0.0038	.;T
LIST_S2	Benign	0.47	T;T
MetaRNN	Benign	0.0085	T;T
Vest4		0.14

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2743458; hg19: -;