Genetic Variant LRP12:c.-51T>C (chr8-104588948-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_013437.5(LRP12):c.-51T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,364,436 control chromosomes in the GnomAD database, including 15,169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3290 hom., cov: 32)

Exomes 𝑓: 0.13 ( 11879 hom. )

Consequence

LRP12
NM_013437.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.727

Variant links:

Genes affected

LRP12 (HGNC:31708): (LDL receptor related protein 12) This gene encodes a member of the low-density lipoprotein receptor related protein family. The product of this gene is a transmembrane protein that is differentially expressed in many cancer cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

LRP12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 8-104588948-A-G is Benign according to our data. Variant chr8-104588948-A-G is described in ClinVar as [Benign]. Clinvar id is 1240799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP12	NM_013437.5 link	c.-51T>C		5_prime_UTR_variant	Exon 1 of 7	ENST00000276654.10	NP_038465.1	Q9Y561-1Q59H02
LRP12	NM_001135703.3 link	c.-51T>C		5_prime_UTR_variant	Exon 1 of 6		NP_001129175.1	Q9Y561-2Q59H02

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRP12	ENST00000276654.10 link	c.-51T>C	5_prime_UTR_variant	Exon 1 of 7	1	NM_013437.5	ENSP00000276654.5	Q9Y561-1
LRP12	ENST00000520770.1 link	n.62T>C	non_coding_transcript_exon_variant	Exon 1 of 4	1
LRP12	ENST00000424843.6 link	c.-51T>C	5_prime_UTR_variant	Exon 1 of 6	2		ENSP00000399148.2	Q9Y561-2
LRP12	ENST00000519675.1 link	n.48T>C	non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

27896

AN:

146242

Hom.:

3275

Cov.:

show subpopulations

Gnomad AFR

AF:

0.349

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.147

Gnomad EAS

AF:

0.0575

Gnomad SAS

AF:

0.181

Gnomad FIN

AF:

0.198

Gnomad MID

AF:

0.147

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.168

GnomAD3 exomes

AF:

0.0864

AC:

10453

AN:

120950

Hom.:

990

AF XY:

0.0844

AC XY:

5499

AN XY:

65116

show subpopulations

Gnomad AFR exome

AF:

0.266

Gnomad AMR exome

AF:

0.0681

Gnomad ASJ exome

AF:

0.0454

Gnomad EAS exome

AF:

0.0370

Gnomad SAS exome

AF:

0.117

Gnomad FIN exome

AF:

0.150

Gnomad NFE exome

AF:

0.0593

Gnomad OTH exome

AF:

0.0822

GnomAD4 exome

AF:

0.126

AC:

154036

AN:

1218096

Hom.:

11879

Cov.:

AF XY:

0.128

AC XY:

77938

AN XY:

609286

show subpopulations

Gnomad4 AFR exome

AF:

0.349

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.143

Gnomad4 EAS exome

AF:

0.0403

Gnomad4 SAS exome

AF:

0.175

Gnomad4 FIN exome

AF:

0.185

Gnomad4 NFE exome

AF:

0.115

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.191

AC:

27966

AN:

146340

Hom.:

3290

Cov.:

AF XY:

0.192

AC XY:

13686

AN XY:

71314

show subpopulations

Gnomad4 AFR

AF:

0.349

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.147

Gnomad4 EAS

AF:

0.0577

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.198

Gnomad4 NFE

AF:

0.120

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.162

Hom.:

297

Bravo

AF:

0.185

Asia WGS

AF:

0.157

AC:

543

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 29, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27142828) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.69

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