4-3531339-C-T

Variant names:

• chr4-3531339-C-T
• rs1794429
• NM_002337.4:c.204+870G>A

Variant summary

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

The NM_002337.4(LRPAP1):​c.204+870G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 152,036 control chromosomes in the GnomAD database, including 36,243 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 0.68 (36243 hom., cov: 32)
• Consequence: LRPAP1 NM_002337.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRPAP1	NM_002337.4	c.204+870G>A		intron_variant	Intron 1 of 7	ENST00000650182.1	NP_002328.1
LRPAP1	NR_110005.2	n.167+644G>A		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRPAP1	ENST00000650182.1	c.204+870G>A		intron_variant	Intron 1 of 7		NM_002337.4	ENSP00000497444.1

Frequencies

GnomAD3 genomes AF: 0.684 AC: 103858 AN: 151918 Hom.: 36197 Cov.: 32

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.921

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.684 AC: 103957 AN: 152036 Hom.: 36243 Cov.: 32 AF XY: 0.691 AC XY: 51337 AN XY: 74316

African (AFR) AF: 0.565 AC: 23435 AN: 41452

American (AMR) AF: 0.776 AC: 11871 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2545 AN: 3472

East Asian (EAS) AF: 0.921 AC: 4754 AN: 5160

South Asian (SAS) AF: 0.805 AC: 3877 AN: 4816

European-Finnish (FIN) AF: 0.746 AC: 7897 AN: 10580

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47110 AN: 67950

Other (OTH) AF: 0.701 AC: 1482 AN: 2114

Alfa AF: 0.697 Hom.: 9392

Bravo AF: 0.680

Asia WGS AF: 0.835 AC: 2904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.79
PhyloP100		-0.18
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: rs1794429; hg19: chr4-3533066;