rs3468

Variant names:

• chr4-3503721-G-A
• rs3468
• NM_002337.4:c.*9253C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-3503721-G-A
• chr4-3503721-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 28 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=-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 rank	MANE	Protein	UniProt
LRPAP1	NM_002337.4	c.*9253C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000650182.1	NP_002328.1
LRPAP1	NR_110005.2	n.10290C>T		non_coding_transcript_exon_variant	Exon 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRPAP1	ENST00000650182.1	c.*9253C>T		3_prime_UTR_variant	Exon 8 of 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 3 AN: 6

Other (OTH) AF: 0.167 AC: 1 AN: 6

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

African (AFR) AF: 0.212 AC: 8825 AN: 41542

American (AMR) AF: 0.272 AC: 4162 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1267 AN: 3472

East Asian (EAS) AF: 0.519 AC: 2687 AN: 5182

South Asian (SAS) AF: 0.286 AC: 1380 AN: 4828

European-Finnish (FIN) AF: 0.483 AC: 5106 AN: 10574

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.350 AC: 23836 AN: 68006

Other (OTH) AF: 0.352 AC: 742 AN: 2110

Alfa AF: 0.329 Hom.: 14887

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
PhyloP100		-0.73

Splicing

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

Other links and lift over

dbSNP: rs3468; hg19: chr4-3505448;