dbSNP rs6789: LRPAP1:n.1043T>C (chr4-3512968-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000296325.9(LRPAP1):n.1043T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,605,270 control chromosomes in the GnomAD database, including 90,580 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 0.33 ( 8484 hom., cov: 34)

Exomes 𝑓: 0.33 ( 82096 hom. )

Consequence

LRPAP1
ENST00000296325.9 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.298

Publications

25 publications found

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 Gene-Disease associations (from GenCC):

myopia 23, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

LRPAP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRPAP1	NM_002337.4 link	c.*6T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000650182.1	NP_002328.1
LRPAP1	NR_110005.2 link	n.1043T>C		non_coding_transcript_exon_variant	Exon 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRPAP1	ENST00000296325.9 link	n.1043T>C		non_coding_transcript_exon_variant	Exon 8 of 8	1
LRPAP1	ENST00000650182.1 link	c.*6T>C		3_prime_UTR_variant	Exon 8 of 8		NM_002337.4	ENSP00000497444.1

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

49472

AN:

152044

Hom.:

8465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.409

Gnomad SAS

AF:

0.503

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.311

GnomAD2 exomes

AF:

0.366

AC:

86976

AN:

237522

AF XY:

0.365

show subpopulations

Gnomad AFR exome

AF:

0.271

Gnomad AMR exome

AF:

0.584

Gnomad ASJ exome

AF:

0.290

Gnomad EAS exome

AF:

0.413

Gnomad FIN exome

AF:

0.242

Gnomad NFE exome

AF:

0.302

Gnomad OTH exome

AF:

0.343

GnomAD4 exome

AF:

0.328

AC:

477109

AN:

1453108

Hom.:

82096

Cov.:

AF XY:

0.333

AC XY:

240718

AN XY:

722226

show subpopulations

African (AFR)

AF:

0.286

AC:

9515

AN:

33258

American (AMR)

AF:

0.573

AC:

24903

AN:

43490

Ashkenazi Jewish (ASJ)

AF:

0.287

AC:

7474

AN:

26004

East Asian (EAS)

AF:

0.413

AC:

16217

AN:

39258

South Asian (SAS)

AF:

0.508

AC:

42968

AN:

84570

European-Finnish (FIN)

AF:

0.243

AC:

12858

AN:

52916

Middle Eastern (MID)

AF:

0.354

AC:

2035

AN:

5744

European-Non Finnish (NFE)

AF:

0.308

AC:

341335

AN:

1107770

Other (OTH)

AF:

0.330

AC:

19804

AN:

60098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

14073

28146

42219

56292

70365

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11414

22828

34242

45656

57070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.325

AC:

49528

AN:

152162

Hom.:

8484

Cov.:

AF XY:

0.331

AC XY:

24661

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.285

AC:

11843

AN:

41518

American (AMR)

AF:

0.475

AC:

7267

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

1042

AN:

3470

East Asian (EAS)

AF:

0.410

AC:

2122

AN:

5180

South Asian (SAS)

AF:

0.502

AC:

2420

AN:

4820

European-Finnish (FIN)

AF:

0.247

AC:

2611

AN:

10570

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.311

AC:

21152

AN:

67984

Other (OTH)

AF:

0.309

AC:

653

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1763

3526

5289

7052

8815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.320

Hom.:

19087

Bravo

AF:

0.337

Asia WGS

AF:

0.407

AC:

1413

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.80

(source)

DANN

Benign

0.50

PhyloP100

-0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over