2-141409668-T-A

Variant names:

• chr2-141409668-T-A
• rs6429874
• NM_018557.3:c.343+70728A>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.343+70728A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 151,868 control chromosomes in the GnomAD database, including 33,406 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 (33406 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.650
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.343+70728A>T		intron_variant	Intron 3 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.-48+70728A>T		intron_variant	Intron 3 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.454+70728A>T		intron_variant	Intron 3 of 76		XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.343+70728A>T		intron_variant	Intron 3 of 90	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000434794.1	c.205+400611A>T		intron_variant	Intron 2 of 13	2		ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98822 AN: 151748 Hom.: 33407 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.651 AC: 98854 AN: 151868 Hom.: 33406 Cov.: 32 AF XY: 0.647 AC XY: 48023 AN XY: 74200

African (AFR) AF: 0.493 AC: 20418 AN: 41392

American (AMR) AF: 0.651 AC: 9953 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2507 AN: 3466

East Asian (EAS) AF: 0.375 AC: 1935 AN: 5154

South Asian (SAS) AF: 0.636 AC: 3074 AN: 4830

European-Finnish (FIN) AF: 0.758 AC: 8001 AN: 10560

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50588 AN: 67874

Other (OTH) AF: 0.663 AC: 1397 AN: 2108

Alfa AF: 0.700 Hom.: 4698

Bravo AF: 0.633

Asia WGS AF: 0.528 AC: 1833 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.0
DANN	Benign	0.83
PhyloP100		0.65
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: rs6429874; hg19: chr2-142167237;