chr4-3512812-G-A

Variant names:

• chr4-3512812-G-A
• rs1049574
• NM_002337.4:c.*162C>T

Variant summary

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

The ENST00000650182.1(LRPAP1):​c.*162C>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 0.241 in 615,146 control chromosomes in the GnomAD database, including 20,348 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 0.23 (4372 hom., cov: 33)
  • Exomes 𝑓: 0.25 (15976 hom.)
• Consequence: LRPAP1 ENST00000650182.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.571
• Publications: 18 publications found

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 Gene-Disease associations (from GenCC):

• myopia 23, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000650182.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRPAP1	NM_002337.4	MANE Select	c.*162C>T		3_prime_UTR	Exon 8 of 8	NP_002328.1
	LRPAP1	NR_110005.2		n.1199C>T		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRPAP1	ENST00000650182.1	MANE Select	c.*162C>T		3_prime_UTR	Exon 8 of 8	ENSP00000497444.1
	LRPAP1	ENST00000296325.9	TSL:1	n.*121C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34611 AN: 151970 Hom.: 4377 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.246 AC: 113790 AN: 463058 Hom.: 15976 Cov.: 5 AF XY: 0.243 AC XY: 58926 AN XY: 242750

African (AFR) AF: 0.188 AC: 2385 AN: 12688

American (AMR) AF: 0.153 AC: 2881 AN: 18794

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 3048 AN: 13806

East Asian (EAS) AF: 0.520 AC: 15956 AN: 30686

South Asian (SAS) AF: 0.206 AC: 9502 AN: 46120

European-Finnish (FIN) AF: 0.383 AC: 11365 AN: 29696

Middle Eastern (MID) AF: 0.151 AC: 302 AN: 2002

European-Non Finnish (NFE) AF: 0.220 AC: 62121 AN: 282962

Other (OTH) AF: 0.237 AC: 6230 AN: 26304

GnomAD4 genome AF: 0.228 AC: 34618 AN: 152088 Hom.: 4372 Cov.: 33 AF XY: 0.233 AC XY: 17325 AN XY: 74336

African (AFR) AF: 0.187 AC: 7773 AN: 41484

American (AMR) AF: 0.169 AC: 2579 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 744 AN: 3472

East Asian (EAS) AF: 0.513 AC: 2644 AN: 5154

South Asian (SAS) AF: 0.224 AC: 1078 AN: 4822

European-Finnish (FIN) AF: 0.386 AC: 4074 AN: 10566

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14975 AN: 67986

Other (OTH) AF: 0.221 AC: 467 AN: 2110

Alfa AF: 0.207 Hom.: 4434

Bravo AF: 0.210

Asia WGS AF: 0.371 AC: 1293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.56
PhyloP100		-0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1049574; hg19: chr4-3514539; COSMIC: COSV56346216; COSMIC: COSV56346216;