chr4-3513211-A-G

Position:

• chr4-3513211-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• 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/exons	MANE	Protein	UniProt
LRPAP1	NM_002337.4	c.1012-175T>C		intron_variant		ENST00000650182.1	NP_002328.1
LRPAP1	NR_110005.2	n.975-175T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRPAP1	ENST00000650182.1	c.1012-175T>C		intron_variant			NM_002337.4	ENSP00000497444	P1
LRPAP1	ENST00000296325.9	n.975-175T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.791

Gnomad4 ASJ AF: 0.737

Gnomad4 EAS AF: 0.928

Gnomad4 SAS AF: 0.812

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.727

Alfa AF: 0.697 Hom.: 4371

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

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: rs1741553; hg19: chr4-3514938;