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GeneBe

4-3514824-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_002337.4(LRPAP1):c.939C>T(p.Asp313=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000894 in 1,613,462 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 4 hom., cov: 35)
Exomes 𝑓: 0.00049 ( 3 hom. )

Consequence

LRPAP1
NM_002337.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.51
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-3514824-G-A is Benign according to our data. Variant chr4-3514824-G-A is described in ClinVar as [Benign]. Clinvar id is 784487.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.51 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0048 (732/152368) while in subpopulation AFR AF= 0.0165 (688/41590). AF 95% confidence interval is 0.0155. There are 4 homozygotes in gnomad4. There are 337 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRPAP1NM_002337.4 linkuse as main transcriptc.939C>T p.Asp313= synonymous_variant 7/8 ENST00000650182.1
LRPAP1NR_110005.2 linkuse as main transcriptn.902C>T non_coding_transcript_exon_variant 7/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRPAP1ENST00000650182.1 linkuse as main transcriptc.939C>T p.Asp313= synonymous_variant 7/8 NM_002337.4 P1
LRPAP1ENST00000296325.9 linkuse as main transcriptn.902C>T non_coding_transcript_exon_variant 7/81
LRPAP1ENST00000648517.1 linkuse as main transcript downstream_gene_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00482
AC:
734
AN:
152250
Hom.:
4
Cov.:
35
show subpopulations
Gnomad AFR
AF:
0.0166
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00222
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00127
AC:
319
AN:
250878
Hom.:
5
AF XY:
0.000810
AC XY:
110
AN XY:
135742
show subpopulations
Gnomad AFR exome
AF:
0.0184
Gnomad AMR exome
AF:
0.000463
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000487
AC:
711
AN:
1461094
Hom.:
3
Cov.:
34
AF XY:
0.000399
AC XY:
290
AN XY:
726898
show subpopulations
Gnomad4 AFR exome
AF:
0.0174
Gnomad4 AMR exome
AF:
0.000470
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.0000189
Gnomad4 NFE exome
AF:
0.0000216
Gnomad4 OTH exome
AF:
0.00116
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00480
AC:
732
AN:
152368
Hom.:
4
Cov.:
35
AF XY:
0.00452
AC XY:
337
AN XY:
74514
show subpopulations
Gnomad4 AFR
AF:
0.0165
Gnomad4 AMR
AF:
0.00222
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00241
Hom.:
1
Bravo
AF:
0.00548
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 23, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
12
Dann
Benign
0.88
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs35919694; hg19: chr4-3516551; API