2-140256350-C-T

Variant names:

• chr2-140256350-C-T
• rs13021003
• NM_018557.3:c.13248-9188G>A

Variant summary

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

The NM_018557.3(LRP1B):​c.13248-9188G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 150,946 control chromosomes in the GnomAD database, including 29,247 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 0.61 (29247 hom., cov: 27)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 4 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]

ENSG00000300471 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.13248-9188G>A		intron_variant	Intron 86 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.12858-9188G>A		intron_variant	Intron 86 of 90		XP_016859830.1
LRP1B	XM_017004342.1	c.8100-9188G>A		intron_variant	Intron 57 of 61		XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.13248-9188G>A		intron_variant	Intron 86 of 90	1	NM_018557.3	ENSP00000374135.3

Frequencies

GnomAD3 genomes AF: 0.613 AC: 92494 AN: 150828 Hom.: 29230 Cov.: 27

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.613 AC: 92555 AN: 150946 Hom.: 29247 Cov.: 27 AF XY: 0.612 AC XY: 45086 AN XY: 73722

African (AFR) AF: 0.463 AC: 19023 AN: 41088

American (AMR) AF: 0.575 AC: 8693 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1946 AN: 3466

East Asian (EAS) AF: 0.683 AC: 3491 AN: 5108

South Asian (SAS) AF: 0.560 AC: 2673 AN: 4776

European-Finnish (FIN) AF: 0.722 AC: 7457 AN: 10328

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.697 AC: 47212 AN: 67758

Other (OTH) AF: 0.590 AC: 1233 AN: 2090

Alfa AF: 0.654 Hom.: 38272

Bravo AF: 0.598

Asia WGS AF: 0.582 AC: 2020 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.040
DANN	Benign	0.33
PhyloP100		-1.5
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: rs13021003; hg19: chr2-141013919;