rs9694676

chr8-104588948-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.727

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
LRP12	NM_013437.5	c.-51T>C		5_prime_UTR_variant	1/7	ENST00000276654.10
LRP12	NM_001135703.3	c.-51T>C		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP12	ENST00000276654.10	c.-51T>C		5_prime_UTR_variant	1/7	1	NM_013437.5	P4
LRP12	ENST00000520770.1	n.62T>C		non_coding_transcript_exon_variant	1/4	1
LRP12	ENST00000424843.6	c.-51T>C		5_prime_UTR_variant	1/6	2		A1
LRP12	ENST00000519675.1	n.48T>C		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.191 AC: 27896 AN: 146242 Hom.: 3275 Cov.: 32

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

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.: 17 AF XY: 0.128 AC XY: 77938 AN XY: 609286

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.: 32 AF XY: 0.192 AC XY: 13686 AN XY: 71314

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 29, 2020

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	18
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

Other links and lift over

dbSNP: rs9694676; hg19: chr8-105601176; COSMIC: COSV52626852; COSMIC: COSV52626852;