2-140984021-T-C

Position:

• chr2-140984021-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000389484.8(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 ENST00000389484.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.2771-1745A>G		intron_variant		ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.2381-1745A>G		intron_variant			XP_016859830.1
LRP1B	XM_047444771.1	c.2882-1745A>G		intron_variant			XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.2771-1745A>G		intron_variant		1	NM_018557.3	ENSP00000374135	P1
LRP1B	ENST00000434794.1	c.206-1745A>G		intron_variant		2		ENSP00000413239

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

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.164

Alfa AF: 0.128 Hom.: 128

Bravo AF: 0.137

Asia WGS AF: 0.162 AC: 552 AN: 3406

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	10
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs4954683; hg19: chr2-141741590;