ENST00000520770.1:n.62T>C

Variant names:

• chr8-104588948-A-G
• rs9694676
• ENST00000520770.1:n.62T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000520770.1(LRP12):​n.62T>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 0.133 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 ENST00000520770.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.727
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• oculopharyngodistal myopathy 1

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520770.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP12	NM_013437.5	MANE Select	c.-51T>C		5_prime_UTR	Exon 1 of 7	NP_038465.1
	LRP12	NM_001135703.3		c.-51T>C		5_prime_UTR	Exon 1 of 6	NP_001129175.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP12	ENST00000520770.1	TSL:1	n.62T>C		non_coding_transcript_exon	Exon 1 of 4
	LRP12	ENST00000276654.10	TSL:1 MANE Select	c.-51T>C		5_prime_UTR	Exon 1 of 7	ENSP00000276654.5
	LRP12	ENST00000519675.1	TSL:2	n.48T>C		non_coding_transcript_exon	Exon 1 of 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

GnomAD2 exomes AF: 0.0864 AC: 10453 AN: 120950 AF XY: 0.0844

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 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

African (AFR) AF: 0.349 AC: 9352 AN: 26766

American (AMR) AF: 0.104 AC: 3212 AN: 30972

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 3302 AN: 23094

East Asian (EAS) AF: 0.0403 AC: 1337 AN: 33166

South Asian (SAS) AF: 0.175 AC: 12448 AN: 71274

European-Finnish (FIN) AF: 0.185 AC: 9076 AN: 49154

Middle Eastern (MID) AF: 0.176 AC: 891 AN: 5074

European-Non Finnish (NFE) AF: 0.115 AC: 107078 AN: 927270

Other (OTH) AF: 0.143 AC: 7340 AN: 51326

GnomAD4 genome AF: 0.191 AC: 27966 AN: 146340 Hom.: 3290 Cov.: 32 AF XY: 0.192 AC XY: 13686 AN XY: 71314

African (AFR) AF: 0.349 AC: 13952 AN: 39928

American (AMR) AF: 0.136 AC: 1929 AN: 14150

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 502 AN: 3410

East Asian (EAS) AF: 0.0577 AC: 268 AN: 4646

South Asian (SAS) AF: 0.183 AC: 839 AN: 4592

European-Finnish (FIN) AF: 0.198 AC: 1990 AN: 10034

Middle Eastern (MID) AF: 0.151 AC: 42 AN: 278

European-Non Finnish (NFE) AF: 0.120 AC: 7972 AN: 66394

Other (OTH) AF: 0.167 AC: 337 AN: 2016

Alfa AF: 0.168 Hom.: 339

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	18
DANN	Benign	0.69
PhyloP100		0.73
PromoterAI		0.25	Neutral
Mutation Taster		=296/4	polymorphism (auto)

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

Other links and lift over

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