2-140814540-G-T

Position:

• chr2-140814540-G-T

Variant summary

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

The NM_018557.3(LRP1B):​c.5210-734C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0964 in 152,136 control chromosomes in the GnomAD database, including 1,019 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 0.096 (1019 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.5210-734C>A		intron_variant		ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.4820-734C>A		intron_variant			XP_016859830.1
LRP1B	XM_017004342.1	c.62-734C>A		intron_variant			XP_016859831.1
LRP1B	XM_047444771.1	c.5321-734C>A		intron_variant			XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.5210-734C>A		intron_variant		1	NM_018557.3	ENSP00000374135	P1

Frequencies

GnomAD3 genomes AF: 0.0965 AC: 14669 AN: 152018 Hom.: 1019 Cov.: 32

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.0870

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.0927

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

GnomAD4 genome AF: 0.0964 AC: 14667 AN: 152136 Hom.: 1019 Cov.: 32 AF XY: 0.0994 AC XY: 7390 AN XY: 74378

Gnomad4 AFR AF: 0.0242

Gnomad4 AMR AF: 0.0770

Gnomad4 ASJ AF: 0.0870

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.201

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.0918

Alfa AF: 0.123 Hom.: 664

Bravo AF: 0.0827

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.9
DANN	Benign	0.82

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: rs13432282; hg19: chr2-141572109;