2-140512305-T-C

Variant names:

• chr2-140512305-T-C
• rs1463615
• NM_018557.3:c.8270-2249A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The NM_018557.3(LRP1B):​c.8270-2249A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,006 control chromosomes in the GnomAD database, including 41,842 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 0.74 (41842 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.76
• 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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.8270-2249A>G		intron_variant	Intron 51 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.7880-2249A>G		intron_variant	Intron 51 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.8381-2249A>G		intron_variant	Intron 51 of 76		XP_047300727.1
LRP1B	XM_017004342.1	c.3122-2249A>G		intron_variant	Intron 22 of 61		XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.8270-2249A>G		intron_variant	Intron 51 of 90	1	NM_018557.3	ENSP00000374135.3

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111777 AN: 151888 Hom.: 41808 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.736 AC: 111864 AN: 152006 Hom.: 41842 Cov.: 32 AF XY: 0.727 AC XY: 54021 AN XY: 74280

African (AFR) AF: 0.819 AC: 33964 AN: 41470

American (AMR) AF: 0.756 AC: 11547 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2762 AN: 3472

East Asian (EAS) AF: 0.441 AC: 2278 AN: 5166

South Asian (SAS) AF: 0.621 AC: 2992 AN: 4818

European-Finnish (FIN) AF: 0.621 AC: 6549 AN: 10540

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49324 AN: 67956

Other (OTH) AF: 0.759 AC: 1602 AN: 2112

Alfa AF: 0.738 Hom.: 51354

Bravo AF: 0.751

Asia WGS AF: 0.572 AC: 1989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	18
DANN	Benign	0.90
PhyloP100		2.8
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: rs1463615; hg19: chr2-141269874;