Variant 8-104497472-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000276654.10(LRP12):c.1080T>C(p.Asn360=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00766 in 1,614,148 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0080 ( 56 hom. )

Consequence

LRP12
ENST00000276654.10 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.211

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 8-104497472-A-G is Benign according to our data. Variant chr8-104497472-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1335717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.211 with no splicing effect.

BS2

High AC in GnomAd4 at 701 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP12	NM_013437.5 linkuse as main transcript	c.1080T>C	p.Asn360=	synonymous_variant	5/7	ENST00000276654.10	NP_038465.1
LRP12	NM_001135703.3 linkuse as main transcript	c.1023T>C	p.Asn341=	synonymous_variant	4/6		NP_001129175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP12	ENST00000276654.10 linkuse as main transcript	c.1080T>C	p.Asn360=	synonymous_variant	5/7	1	NM_013437.5	ENSP00000276654	P4	Q9Y561-1
LRP12	ENST00000424843.6 linkuse as main transcript	c.1023T>C	p.Asn341=	synonymous_variant	4/6	2		ENSP00000399148	A1	Q9Y561-2
LRP12	ENST00000523007.1 linkuse as main transcript	c.-154T>C		5_prime_UTR_variant	1/3	2		ENSP00000429305

Frequencies

GnomAD3 genomes

AF:

0.00461

AC:

701

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00761

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00491

AC:

1235

AN:

251310

Hom.:

AF XY:

0.00476

AC XY:

646

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00269

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00186

Gnomad FIN exome

AF:

0.00568

Gnomad NFE exome

AF:

0.00797

Gnomad OTH exome

AF:

0.00588

GnomAD4 exome

AF:

0.00798

AC:

11660

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00779

AC XY:

5664

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00273

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00211

Gnomad4 FIN exome

AF:

0.00616

Gnomad4 NFE exome

AF:

0.00963

Gnomad4 OTH exome

AF:

0.00475

GnomAD4 genome

AF:

0.00460

AC:

701

AN:

152288

Hom.:

Cov.:

AF XY:

0.00436

AC XY:

325

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00471

Gnomad4 NFE

AF:

0.00762

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00647

Hom.:

Bravo

AF:

0.00432

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00774

EpiControl

AF:

0.00717

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	LRP12: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.16

DANN

Benign

0.44

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