NM_018557.3:c.1014-62253A>T

Variant names:

• chr2-141124526-T-A
• rs10928098
• NM_018557.3:c.1014-62253A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018557.3(LRP1B):​c.1014-62253A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,858 control chromosomes in the GnomAD database, including 9,533 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 0.35 (9533 hom., cov: 30)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.804
• Publications: 2 publications found

Genes affected

LRP1B (HGNC:6693): (LDL receptor related protein 1B) This gene encodes a member of the low density lipoprotein (LDL) receptor family. These receptors play a wide variety of roles in normal cell function and development due to their interactions with multiple ligands. Disruption of this gene has been reported in several types of cancer. [provided by RefSeq, Jun 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018557.3. 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
	LRP1B	NM_018557.3	MANE Select	c.1014-62253A>T		intron	N/A	NP_061027.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	ENST00000389484.8	TSL:1 MANE Select	c.1014-62253A>T		intron	N/A	ENSP00000374135.3
	LRP1B	ENST00000434794.1	TSL:2	c.206-142250A>T		intron	N/A	ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52618 AN: 151740 Hom.: 9527 Cov.: 30

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.343

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.347 AC: 52651 AN: 151858 Hom.: 9533 Cov.: 30 AF XY: 0.356 AC XY: 26415 AN XY: 74186

African (AFR) AF: 0.268 AC: 11104 AN: 41450

American (AMR) AF: 0.408 AC: 6213 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1086 AN: 3470

East Asian (EAS) AF: 0.495 AC: 2550 AN: 5150

South Asian (SAS) AF: 0.388 AC: 1864 AN: 4810

European-Finnish (FIN) AF: 0.501 AC: 5262 AN: 10508

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23526 AN: 67926

Other (OTH) AF: 0.342 AC: 724 AN: 2114

Alfa AF: 0.353 Hom.: 1215

Bravo AF: 0.338

Asia WGS AF: 0.424 AC: 1468 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.3
DANN	Benign	0.35
PhyloP100		0.80
Mutation Taster		=100/0	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: rs10928098; hg19: chr2-141882095;