22-25366043-T-C

Variant names:

• chr22-25366043-T-C
• rs713878
• XR_007068030.1:n.9988A>G

Variant summary

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

The XR_007068030.1(LRP5L):​n.9988A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 151,780 control chromosomes in the GnomAD database, including 16,740 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 0.46 (16740 hom., cov: 34)
• Consequence: LRP5L XR_007068030.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368
• Publications: 5 publications found

Genes affected

LRP5L (HGNC:25323): (LDL receptor related protein 5 like (pseudogene)) Predicted to enable coreceptor activity. Predicted to be involved in several processes, including animal organ development; cholesterol homeostasis; and osteoblast development. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000290796 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP5L	XR_007068030.1	n.9988A>G		non_coding_transcript_exon_variant	Exon 4 of 7
LRP5L	XR_007068031.1	n.10240A>G		non_coding_transcript_exon_variant	Exon 3 of 6
LRP5L	XR_005228024.2	n.602-3652A>G		intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000290796	ENST00000444995.7	n.571-5820A>G		intron_variant	Intron 3 of 6	5
ENSG00000290796	ENST00000468442.1	n.348-4724A>G		intron_variant	Intron 2 of 3	3
ENSG00000290796	ENST00000650168.1	n.703-5820A>G		intron_variant	Intron 4 of 7
LRP5L	ENST00000650500.2	n.600-5820A>G		intron_variant	Intron 4 of 7

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69321 AN: 151662 Hom.: 16736 Cov.: 34

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.457 AC: 69341 AN: 151780 Hom.: 16740 Cov.: 34 AF XY: 0.457 AC XY: 33879 AN XY: 74174

African (AFR) AF: 0.290 AC: 11979 AN: 41378

American (AMR) AF: 0.376 AC: 5743 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1836 AN: 3468

East Asian (EAS) AF: 0.446 AC: 2292 AN: 5136

South Asian (SAS) AF: 0.626 AC: 3005 AN: 4800

European-Finnish (FIN) AF: 0.510 AC: 5380 AN: 10546

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37456 AN: 67872

Other (OTH) AF: 0.486 AC: 1022 AN: 2104

Alfa AF: 0.515 Hom.: 9676

Bravo AF: 0.434

Asia WGS AF: 0.535 AC: 1861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.88
PhyloP100		-0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs713878; hg19: chr22-25762010;