NM_018557.3:c.206-126737G>A

Variant names:

• chr2-141607270-C-T
• rs10496887
• NM_018557.3:c.206-126737G>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.206-126737G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 151,970 control chromosomes in the GnomAD database, including 34,748 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 0.65 (34748 hom., cov: 31)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190
• Publications: 4 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 (NFE) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.206-126737G>A		intron_variant	Intron 2 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.-185-126737G>A		intron_variant	Intron 2 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.317-126737G>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.206-126737G>A		intron_variant	Intron 2 of 90	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000434794.1	c.205+203009G>A		intron_variant	Intron 2 of 13	2		ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98605 AN: 151854 Hom.: 34740 Cov.: 31

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.681

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

GnomAD4 genome AF: 0.649 AC: 98634 AN: 151970 Hom.: 34748 Cov.: 31 AF XY: 0.648 AC XY: 48119 AN XY: 74282

African (AFR) AF: 0.352 AC: 14578 AN: 41398

American (AMR) AF: 0.748 AC: 11433 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2716 AN: 3472

East Asian (EAS) AF: 0.662 AC: 3407 AN: 5148

South Asian (SAS) AF: 0.551 AC: 2654 AN: 4814

European-Finnish (FIN) AF: 0.763 AC: 8065 AN: 10572

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.785 AC: 53365 AN: 67978

Other (OTH) AF: 0.679 AC: 1428 AN: 2104

Alfa AF: 0.708 Hom.: 6326

Bravo AF: 0.639

Asia WGS AF: 0.573 AC: 1989 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	1.1
DANN	Benign	0.60
PhyloP100		0.19
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: rs10496887; hg19: chr2-142364839;