2-140815172-G-C

Variant names:

• chr2-140815172-G-C
• rs6749707
• NM_018557.3:c.5210-1366C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018557.3(LRP1B):​c.5210-1366C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,686 control chromosomes in the GnomAD database, including 16,907 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 0.46 (16907 hom., cov: 30)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960
• Publications: 5 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 = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.5210-1366C>G		intron_variant	Intron 31 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.4820-1366C>G		intron_variant	Intron 31 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.5321-1366C>G		intron_variant	Intron 31 of 76		XP_047300727.1
LRP1B	XM_017004342.1	c.62-1366C>G		intron_variant	Intron 2 of 61		XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.5210-1366C>G		intron_variant	Intron 31 of 90	1	NM_018557.3	ENSP00000374135.3

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69103 AN: 151568 Hom.: 16905 Cov.: 30

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.456 AC: 69144 AN: 151686 Hom.: 16907 Cov.: 30 AF XY: 0.454 AC XY: 33653 AN XY: 74110

African (AFR) AF: 0.277 AC: 11449 AN: 41370

American (AMR) AF: 0.434 AC: 6614 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2037 AN: 3470

East Asian (EAS) AF: 0.580 AC: 2987 AN: 5146

South Asian (SAS) AF: 0.463 AC: 2224 AN: 4802

European-Finnish (FIN) AF: 0.491 AC: 5137 AN: 10458

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37025 AN: 67868

Other (OTH) AF: 0.470 AC: 992 AN: 2112

Alfa AF: 0.340 Hom.: 936

Bravo AF: 0.441

Asia WGS AF: 0.516 AC: 1796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.72
PhyloP100		-0.96
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: rs6749707; hg19: chr2-141572741;