2-140984021-T-C

Variant names:

• chr2-140984021-T-C
• rs4954683
• NM_018557.3:c.2771-1745A>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.2771-1745A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 151,786 control chromosomes in the GnomAD database, including 1,429 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 0.14 (1429 hom., cov: 33)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018557.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	NM_018557.3	MANE Select	c.2771-1745A>G		intron	N/A	NP_061027.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	ENST00000389484.8	TSL:1 MANE Select	c.2771-1745A>G		intron	N/A	ENSP00000374135.3
	LRP1B	ENST00000434794.1	TSL:2	c.206-1745A>G		intron	N/A	ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20648 AN: 151654 Hom.: 1426 Cov.: 33

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.136 AC: 20655 AN: 151786 Hom.: 1429 Cov.: 33 AF XY: 0.135 AC XY: 10017 AN XY: 74204

African (AFR) AF: 0.132 AC: 5496 AN: 41516

American (AMR) AF: 0.113 AC: 1725 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 633 AN: 3472

East Asian (EAS) AF: 0.197 AC: 1014 AN: 5154

South Asian (SAS) AF: 0.197 AC: 944 AN: 4804

European-Finnish (FIN) AF: 0.108 AC: 1143 AN: 10564

Middle Eastern (MID) AF: 0.176 AC: 39 AN: 222

European-Non Finnish (NFE) AF: 0.136 AC: 9204 AN: 67828

Other (OTH) AF: 0.164 AC: 342 AN: 2090

Alfa AF: 0.130 Hom.: 345

Bravo AF: 0.137

Asia WGS AF: 0.162 AC: 552 AN: 3406

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	10
DANN	Benign	0.70
PhyloP100		2.3
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: rs4954683; hg19: chr2-141741590;