rs9624808

chr22-25374065-G-Achr22-25374065-G-C

Variant summary

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

The ENST00000650168.1(ENSG00000290796):n.702+103C>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 0.112 in 152,020 control chromosomes in the GnomAD database, including 1,118 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 0.11 (1118 hom., cov: 32)
• Consequence: ENST00000650168.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP5L	XR_005228030.2	n.601+1748C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000650168.1	n.702+103C>T		intron_variant, non_coding_transcript_variant
LRP5L	ENST00000650500.2	n.599+103C>T		intron_variant, non_coding_transcript_variant
	ENST00000444995.7	n.570+1748C>T		intron_variant, non_coding_transcript_variant		5
	ENST00000468442.1	n.347+1748C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16962 AN: 151904 Hom.: 1111 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0770

Gnomad ASJ AF: 0.0817

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0795

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0943

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

GnomAD4 genome AF: 0.112 AC: 16987 AN: 152020 Hom.: 1118 Cov.: 32 AF XY: 0.111 AC XY: 8284 AN XY: 74342

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.0770

Gnomad4 ASJ AF: 0.0817

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0793

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.0928

Alfa AF: 0.116 Hom.: 193

Bravo AF: 0.103

Asia WGS AF: 0.0410 AC: 146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.64
Dann	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9624808; hg19: chr22-25770032;