chr2-141470756-G-T

Variant names:

• chr2-141470756-G-T
• rs12618990
• NM_018557.3:c.343+9640C>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.343+9640C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,038 control chromosomes in the GnomAD database, including 37,174 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 0.69 (37174 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• 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]

LOC124906079 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.343+9640C>A		intron_variant	Intron 3 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.-48+9640C>A		intron_variant	Intron 3 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.454+9640C>A		intron_variant	Intron 3 of 76		XP_047300727.1
LOC124906079	XR_007087248.1	n.58-281G>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.343+9640C>A		intron_variant	Intron 3 of 90	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000434794.1	c.205+339523C>A		intron_variant	Intron 2 of 13	2		ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104164 AN: 151920 Hom.: 37154 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.719

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

GnomAD4 genome AF: 0.686 AC: 104232 AN: 152038 Hom.: 37174 Cov.: 32 AF XY: 0.687 AC XY: 51077 AN XY: 74300

African (AFR) AF: 0.472 AC: 19565 AN: 41444

American (AMR) AF: 0.757 AC: 11562 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2708 AN: 3472

East Asian (EAS) AF: 0.835 AC: 4321 AN: 5176

South Asian (SAS) AF: 0.581 AC: 2797 AN: 4814

European-Finnish (FIN) AF: 0.773 AC: 8165 AN: 10562

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.774 AC: 52621 AN: 67980

Other (OTH) AF: 0.718 AC: 1518 AN: 2114

Alfa AF: 0.721 Hom.: 15961

Bravo AF: 0.680

Asia WGS AF: 0.666 AC: 2312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.1
DANN	Benign	0.69
PhyloP100		0.14
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: rs12618990; hg19: chr2-142228325;