NM_002337.4:c.204+870G>A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• 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

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.921

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.701

Alfa AF: 0.700 Hom.: 9281

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

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: rs1794429; hg19: chr4-3533066;