rs1049574

Positions:

• chr4-3512812-G-A

Variant summary

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

The NM_002337.4(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 NM_002337.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.571

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRPAP1	NM_002337.4	c.*162C>T		3_prime_UTR_variant	8/8	ENST00000650182.1	NP_002328.1
LRPAP1	NR_110005.2	n.1199C>T		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRPAP1	ENST00000650182.1	c.*162C>T		3_prime_UTR_variant	8/8		NM_002337.4	ENSP00000497444	P1

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

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.153

Gnomad4 ASJ exome AF: 0.221

Gnomad4 EAS exome AF: 0.520

Gnomad4 SAS exome AF: 0.206

Gnomad4 FIN exome AF: 0.383

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.237

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

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.513

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.221

Alfa AF: 0.208 Hom.: 3415

Bravo AF: 0.210

Asia WGS AF: 0.371 AC: 1293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

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