rs133201

Positions:

• chr22-25361301-A-G
• chr22-25361301-A-T

Variant summary

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

The ENST00000467672.5(ENSG00000290796):​n.1257T>C 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 0.765 in 151,888 control chromosomes in the GnomAD database, including 45,140 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 0.76 (45117 hom., cov: 33)
  • Exomes 𝑓: 0.77 (23 hom.)
• Consequence: ENST00000467672.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP5L	XR_005228030.2	n.602-1078T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000650168.1	n.703-1078T>C		intron_variant, non_coding_transcript_variant
LRP5L	ENST00000650500.2	n.600-1078T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116007 AN: 151696 Hom.: 45048 Cov.: 33

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.657

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.759

GnomAD4 exome AF: 0.770 AC: 57 AN: 74 Hom.: 23 Cov.: 0 AF XY: 0.808 AC XY: 42 AN XY: 52

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 0.833

Gnomad4 NFE exome AF: 0.731

Gnomad4 OTH exome AF: 0.875

GnomAD4 genome AF: 0.765 AC: 116136 AN: 151814 Hom.: 45117 Cov.: 33 AF XY: 0.764 AC XY: 56692 AN XY: 74200

Gnomad4 AFR AF: 0.916

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.864

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.760

Alfa AF: 0.705 Hom.: 46162

Bravo AF: 0.769

Asia WGS AF: 0.852 AC: 2965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs133201; hg19: chr22-25757268;