rs5751229

Positions:

• chr22-42149230-G-A
• chr22-42149230-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_938280.2(LOC105377203):​n.222+49C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,190 control chromosomes in the GnomAD database, including 3,679 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 0.21 (3679 hom., cov: 32)
• Consequence: LOC105377203 XR_938280.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108

Genes affected

LOC105377203 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105377203	XR_938280.2	n.222+49C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2D7	ENST00000651010.1	n.177+49C>T		intron_variant, non_coding_transcript_variant
CYP2D7	ENST00000711577.1	n.222+49C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32595 AN: 152072 Hom.: 3677 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.194

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.214 AC: 32599 AN: 152190 Hom.: 3679 Cov.: 32 AF XY: 0.209 AC XY: 15525 AN XY: 74396

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.191

Alfa AF: 0.211 Hom.: 682

Bravo AF: 0.217

Asia WGS AF: 0.250 AC: 873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.29

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5751229; hg19: chr22-42545221;