rs657322

Variant names:

• chr2-140316726-A-G
• rs657322
• NM_018557.3:c.12641-1627T>C

Variant summary

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

The NM_018557.3(LRP1B):​c.12641-1627T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 152,058 control chromosomes in the GnomAD database, including 1,332 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 0.10 (1332 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635
• Publications: 1 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]

ENSG00000300471 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.12641-1627T>C		intron_variant	Intron 82 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.12251-1627T>C		intron_variant	Intron 82 of 90		XP_016859830.1
LRP1B	XM_017004342.1	c.7493-1627T>C		intron_variant	Intron 53 of 61		XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.12641-1627T>C		intron_variant	Intron 82 of 90	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000437977.5	c.1334-1627T>C		intron_variant	Intron 9 of 16	5		ENSP00000415052.1
ENSG00000300471	ENST00000772126.1	n.105-5531A>G		intron_variant	Intron 2 of 3
ENSG00000300471	ENST00000772127.1	n.136-76223A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 15175 AN: 151946 Hom.: 1331 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0549

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0431

Gnomad OTH AF: 0.0774

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

GnomAD4 genome AF: 0.0999 AC: 15193 AN: 152058 Hom.: 1332 Cov.: 32 AF XY: 0.0987 AC XY: 7333 AN XY: 74332

African (AFR) AF: 0.232 AC: 9612 AN: 41428

American (AMR) AF: 0.0548 AC: 835 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 128 AN: 3470

East Asian (EAS) AF: 0.161 AC: 829 AN: 5160

South Asian (SAS) AF: 0.104 AC: 504 AN: 4824

European-Finnish (FIN) AF: 0.0119 AC: 126 AN: 10618

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0431 AC: 2928 AN: 67990

Other (OTH) AF: 0.0780 AC: 165 AN: 2116

Alfa AF: 0.0849 Hom.: 121

Bravo AF: 0.108

Asia WGS AF: 0.162 AC: 564 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.90
DANN	Benign	0.62
PhyloP100		-0.64
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: rs657322; hg19: chr2-141074295;