rs3468

Positions:

• chr4-3503721-G-A
• chr4-3503721-G-T

Variant summary

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

The NM_002337.4(LRPAP1):​c.*9253C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,220 control chromosomes in the GnomAD database, including 8,376 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 0.32 (8375 hom., cov: 34)
  • Exomes 𝑓: 0.36 (1 hom.)
• Consequence: LRPAP1 NM_002337.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.731

Genes affected

LRPAP1 (HGNC:6701): (LDL receptor related protein associated protein 1) This gene encodes a protein that interacts with the low density lipoprotein (LDL) receptor-related protein and facilitates its proper folding and localization by preventing the binding of ligands. Mutations in this gene have been identified in individuals with myopia 23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

LRPAP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRPAP1	NM_002337.4	c.*9253C>T		3_prime_UTR_variant	8/8	ENST00000650182.1	NP_002328.1
LRPAP1	NR_110005.2	n.10290C>T		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRPAP1	ENST00000650182	c.*9253C>T		3_prime_UTR_variant	8/8		NM_002337.4	ENSP00000497444.1

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48506 AN: 152088 Hom.: 8367 Cov.: 34

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.347

GnomAD4 exome AF: 0.357 AC: 5 AN: 14 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.319 AC: 48542 AN: 152206 Hom.: 8375 Cov.: 34 AF XY: 0.322 AC XY: 23984 AN XY: 74406

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.352

Alfa AF: 0.334 Hom.: 12139

Bravo AF: 0.301

Asia WGS AF: 0.417 AC: 1455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.44
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3468; hg19: chr4-3505448;