rs1372256

Variant names:

• chr2-140596827-G-T
• rs1372256
• NM_018557.3:c.7194+1804C>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.7194+1804C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,002 control chromosomes in the GnomAD database, including 3,460 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 0.20 (3460 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.7194+1804C>A		intron_variant	Intron 43 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.6804+1804C>A		intron_variant	Intron 43 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.7305+1804C>A		intron_variant	Intron 43 of 76		XP_047300727.1
LRP1B	XM_017004342.1	c.2046+1804C>A		intron_variant	Intron 14 of 61		XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.7194+1804C>A		intron_variant	Intron 43 of 90	1	NM_018557.3	ENSP00000374135.3

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30349 AN: 151886 Hom.: 3457 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.200 AC: 30367 AN: 152002 Hom.: 3460 Cov.: 32 AF XY: 0.206 AC XY: 15318 AN XY: 74284

African (AFR) AF: 0.131 AC: 5425 AN: 41476

American (AMR) AF: 0.231 AC: 3522 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 715 AN: 3466

East Asian (EAS) AF: 0.372 AC: 1913 AN: 5144

South Asian (SAS) AF: 0.391 AC: 1885 AN: 4822

European-Finnish (FIN) AF: 0.239 AC: 2526 AN: 10556

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13697 AN: 67966

Other (OTH) AF: 0.209 AC: 441 AN: 2110

Alfa AF: 0.201 Hom.: 7965

Bravo AF: 0.191

Asia WGS AF: 0.359 AC: 1251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.0
DANN	Benign	0.63
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1372256; hg19: chr2-141354396;