2-141184250-G-A

Variant names:

• chr2-141184250-G-A
• rs1249426
• NM_018557.3:c.1013+4171C>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.1013+4171C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,854 control chromosomes in the GnomAD database, including 9,142 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 0.34 (9142 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.662 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.1013+4171C>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.1013+4171C>T		intron	N/A	ENSP00000374135.3
	LRP1B	ENST00000434794.1	TSL:2	c.206-201974C>T		intron	N/A	ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51120 AN: 151736 Hom.: 9133 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.337 AC: 51149 AN: 151854 Hom.: 9142 Cov.: 32 AF XY: 0.348 AC XY: 25804 AN XY: 74194

African (AFR) AF: 0.297 AC: 12296 AN: 41444

American (AMR) AF: 0.422 AC: 6418 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 976 AN: 3468

East Asian (EAS) AF: 0.681 AC: 3494 AN: 5134

South Asian (SAS) AF: 0.381 AC: 1838 AN: 4826

European-Finnish (FIN) AF: 0.446 AC: 4714 AN: 10562

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20454 AN: 67884

Other (OTH) AF: 0.322 AC: 679 AN: 2110

Alfa AF: 0.275 Hom.: 1166

Bravo AF: 0.334

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.26
PhyloP100		-0.49
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: rs1249426; hg19: chr2-141941819;