chr2-140979734-C-T

Variant names:

• chr2-140979734-C-T
• rs13032395
• NM_018557.3:c.2887+2426G>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.2887+2426G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,042 control chromosomes in the GnomAD database, including 1,685 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 0.15 (1685 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.37
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.2887+2426G>A		intron_variant	Intron 18 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.2497+2426G>A		intron_variant	Intron 18 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.2998+2426G>A		intron_variant	Intron 18 of 76		XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.2887+2426G>A		intron_variant	Intron 18 of 90	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000434794.1	c.322+2426G>A		intron_variant	Intron 3 of 13	2		ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22244 AN: 151922 Hom.: 1682 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.146 AC: 22258 AN: 152042 Hom.: 1685 Cov.: 32 AF XY: 0.146 AC XY: 10818 AN XY: 74314

African (AFR) AF: 0.159 AC: 6582 AN: 41450

American (AMR) AF: 0.116 AC: 1776 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3470

East Asian (EAS) AF: 0.260 AC: 1343 AN: 5168

South Asian (SAS) AF: 0.197 AC: 952 AN: 4822

European-Finnish (FIN) AF: 0.110 AC: 1169 AN: 10582

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9291 AN: 67968

Other (OTH) AF: 0.172 AC: 363 AN: 2112

Alfa AF: 0.142 Hom.: 560

Bravo AF: 0.148

Asia WGS AF: 0.195 AC: 680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.22
DANN	Benign	0.58
PhyloP100		-3.4
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: rs13032395; hg19: chr2-141737303;