Variant 4-3512969-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_002337.4(LRPAP1):c.*5A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00481 in 1,609,468 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0036 ( 2 hom., cov: 34)

Exomes 𝑓: 0.0049 ( 27 hom. )

Consequence

LRPAP1
NM_002337.4 3_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.01

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 4-3512969-T-C is Benign according to our data. Variant chr4-3512969-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3041339.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRPAP1	NM_002337.4 linkuse as main transcript	c.*5A>G		3_prime_UTR_variant	8/8	ENST00000650182.1	NP_002328.1
LRPAP1	NR_110005.2 linkuse as main transcript	n.1042A>G		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRPAP1	ENST00000650182.1 linkuse as main transcript	c.*5A>G		3_prime_UTR_variant	8/8		NM_002337.4	ENSP00000497444	P1
LRPAP1	ENST00000296325.9 linkuse as main transcript	n.1042A>G		non_coding_transcript_exon_variant	8/8	1

Frequencies

GnomAD3 genomes

AF:

0.00360

AC:

548

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00631

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00394

AC:

952

AN:

241514

Hom.:

AF XY:

0.00383

AC XY:

501

AN XY:

130824

show subpopulations

Gnomad AFR exome

AF:

0.000913

Gnomad AMR exome

AF:

0.00393

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000241

Gnomad FIN exome

AF:

0.00265

Gnomad NFE exome

AF:

0.00644

Gnomad OTH exome

AF:

0.00671

GnomAD4 exome

AF:

0.00494

AC:

7202

AN:

1457114

Hom.:

Cov.:

AF XY:

0.00493

AC XY:

3568

AN XY:

724366

show subpopulations

Gnomad4 AFR exome

AF:

0.000779

Gnomad4 AMR exome

AF:

0.00354

Gnomad4 ASJ exome

AF:

0.000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000318

Gnomad4 FIN exome

AF:

0.00294

Gnomad4 NFE exome

AF:

0.00594

Gnomad4 OTH exome

AF:

0.00389

GnomAD4 genome

AF:

0.00359

AC:

547

AN:

152354

Hom.:

Cov.:

AF XY:

0.00325

AC XY:

242

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00264

Gnomad4 NFE

AF:

0.00629

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00488

Hom.:

Bravo

AF:

0.00336

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LRPAP1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 08, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.082

DANN

Benign

0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over