chr4-3513211-A-G

Variant names:

• chr4-3513211-A-G
• rs1741553
• NM_002337.4:c.1012-175T>C

Variant summary

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

The NM_002337.4(LRPAP1):​c.1012-175T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,246 control chromosomes in the GnomAD database, including 39,158 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 0.71 (39158 hom., cov: 35)
• Consequence: LRPAP1 NM_002337.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRPAP1	NM_002337.4	c.1012-175T>C		intron_variant	Intron 7 of 7	ENST00000650182.1	NP_002328.1
LRPAP1	NR_110005.2	n.975-175T>C		intron_variant	Intron 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRPAP1	ENST00000650182.1	c.1012-175T>C		intron_variant	Intron 7 of 7		NM_002337.4	ENSP00000497444.1
LRPAP1	ENST00000296325.9	n.975-175T>C		intron_variant	Intron 7 of 7	1

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108554 AN: 152128 Hom.: 39101 Cov.: 35

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.928

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.714 AC: 108667 AN: 152246 Hom.: 39158 Cov.: 35 AF XY: 0.720 AC XY: 53606 AN XY: 74444

African (AFR) AF: 0.666 AC: 27675 AN: 41542

American (AMR) AF: 0.791 AC: 12092 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2559 AN: 3472

East Asian (EAS) AF: 0.928 AC: 4801 AN: 5176

South Asian (SAS) AF: 0.812 AC: 3923 AN: 4834

European-Finnish (FIN) AF: 0.747 AC: 7918 AN: 10598

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47170 AN: 68008

Other (OTH) AF: 0.727 AC: 1539 AN: 2116

Alfa AF: 0.696 Hom.: 4542

Bravo AF: 0.714

Asia WGS AF: 0.846 AC: 2943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.37
PhyloP100		-2.0
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: rs1741553; hg19: chr4-3514938;