2-140960077-A-G

Variant names:

• chr2-140960077-A-G
• rs13016717
• NM_018557.3:c.2888-8137T>C

Variant summary

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

The NM_018557.3(LRP1B):​c.2888-8137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 151,636 control chromosomes in the GnomAD database, including 1,688 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 (1688 hom., cov: 31)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.2888-8137T>C		intron_variant	Intron 18 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.2498-8137T>C		intron_variant	Intron 18 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.2999-8137T>C		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.2888-8137T>C		intron_variant	Intron 18 of 90	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000434794.1	c.323-8137T>C		intron_variant	Intron 3 of 13	2		ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22230 AN: 151518 Hom.: 1686 Cov.: 31

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.147 AC: 22245 AN: 151636 Hom.: 1688 Cov.: 31 AF XY: 0.146 AC XY: 10803 AN XY: 74120

African (AFR) AF: 0.153 AC: 6354 AN: 41474

American (AMR) AF: 0.119 AC: 1801 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 618 AN: 3464

East Asian (EAS) AF: 0.269 AC: 1387 AN: 5162

South Asian (SAS) AF: 0.200 AC: 961 AN: 4812

European-Finnish (FIN) AF: 0.115 AC: 1218 AN: 10594

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9369 AN: 67630

Other (OTH) AF: 0.173 AC: 364 AN: 2110

Alfa AF: 0.146 Hom.: 4495

Bravo AF: 0.149

Asia WGS AF: 0.189 AC: 659 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.77
PhyloP100		0.34
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: rs13016717; hg19: chr2-141717646;