rs2381190

Positions:

• chr2-141585130-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018557.3(LRP1B):​c.206-104597T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,058 control chromosomes in the GnomAD database, including 4,991 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 0.23 (4991 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.206-104597T>C		intron_variant		ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.-185-104597T>C		intron_variant			XP_016859830.1
LRP1B	XM_047444771.1	c.317-104597T>C		intron_variant			XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.206-104597T>C		intron_variant		1	NM_018557.3	ENSP00000374135	P1
LRP1B	ENST00000434794.1	c.205+225149T>C		intron_variant		2		ENSP00000413239

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34751 AN: 151940 Hom.: 4991 Cov.: 32

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.229 AC: 34761 AN: 152058 Hom.: 4991 Cov.: 32 AF XY: 0.235 AC XY: 17450 AN XY: 74302

Gnomad4 AFR AF: 0.0617

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.263

Alfa AF: 0.266 Hom.: 2927

Bravo AF: 0.226

Asia WGS AF: 0.340 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs2381190; hg19: chr2-142342699;