2-140788186-T-C

Variant names:

• chr2-140788186-T-C
• rs17515225
• NM_018557.3:c.5360-11948A>G

Variant summary

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

The NM_018557.3(LRP1B):​c.5360-11948A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,052 control chromosomes in the GnomAD database, including 16,198 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 0.44 (16198 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.5360-11948A>G		intron_variant	Intron 32 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.4970-11948A>G		intron_variant	Intron 32 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.5471-11948A>G		intron_variant	Intron 32 of 76		XP_047300727.1
LRP1B	XM_017004342.1	c.212-11948A>G		intron_variant	Intron 3 of 61		XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.5360-11948A>G		intron_variant	Intron 32 of 90	1	NM_018557.3	ENSP00000374135.3

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66211 AN: 151934 Hom.: 16202 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.436 AC: 66224 AN: 152052 Hom.: 16198 Cov.: 32 AF XY: 0.436 AC XY: 32401 AN XY: 74302

African (AFR) AF: 0.202 AC: 8365 AN: 41484

American (AMR) AF: 0.425 AC: 6490 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2026 AN: 3470

East Asian (EAS) AF: 0.657 AC: 3374 AN: 5132

South Asian (SAS) AF: 0.478 AC: 2301 AN: 4814

European-Finnish (FIN) AF: 0.491 AC: 5193 AN: 10570

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36824 AN: 67984

Other (OTH) AF: 0.459 AC: 968 AN: 2110

Alfa AF: 0.456 Hom.: 2251

Bravo AF: 0.417

Asia WGS AF: 0.543 AC: 1888 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.88
PhyloP100		-0.27
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: rs17515225; hg19: chr2-141545755;