NM_018557.3:c.206-7845G>A

Variant names:

• chr2-141488378-C-T
• rs10496882
• NM_018557.3:c.206-7845G>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.206-7845G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 151,946 control chromosomes in the GnomAD database, including 14,892 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 0.42 (14892 hom., cov: 31)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.29
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.206-7845G>A		intron_variant	Intron 2 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.-185-7845G>A		intron_variant	Intron 2 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.317-7845G>A		intron_variant	Intron 2 of 76		XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.206-7845G>A		intron_variant	Intron 2 of 90	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000434794.1	c.205+321901G>A		intron_variant	Intron 2 of 13	2		ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.423 AC: 64251 AN: 151828 Hom.: 14888 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.423 AC: 64279 AN: 151946 Hom.: 14892 Cov.: 31 AF XY: 0.430 AC XY: 31943 AN XY: 74280

African (AFR) AF: 0.235 AC: 9759 AN: 41456

American (AMR) AF: 0.485 AC: 7394 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1778 AN: 3470

East Asian (EAS) AF: 0.708 AC: 3657 AN: 5164

South Asian (SAS) AF: 0.647 AC: 3117 AN: 4814

European-Finnish (FIN) AF: 0.457 AC: 4819 AN: 10548

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32313 AN: 67930

Other (OTH) AF: 0.447 AC: 943 AN: 2108

Alfa AF: 0.464 Hom.: 54994

Bravo AF: 0.416

Asia WGS AF: 0.628 AC: 2184 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.56
PhyloP100		-3.3
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: rs10496882; hg19: chr2-142245947;