chr2-140956076-A-C

Position:

• chr2-140956076-A-C

Variant summary

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

The NM_018557.3(LRP1B):​c.2888-4136T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 151,466 control chromosomes in the GnomAD database, including 28,807 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 0.60 (28807 hom., cov: 31)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP1B	NM_018557.3	c.2888-4136T>G		intron_variant		ENST00000389484.8
LRP1B	XM_017004341.2	c.2498-4136T>G		intron_variant
LRP1B	XM_047444771.1	c.2999-4136T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP1B	ENST00000389484.8	c.2888-4136T>G		intron_variant		1	NM_018557.3	P1
LRP1B	ENST00000434794.1	c.323-4136T>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90175 AN: 151348 Hom.: 28793 Cov.: 31

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.595 AC: 90190 AN: 151466 Hom.: 28807 Cov.: 31 AF XY: 0.601 AC XY: 44486 AN XY: 74032

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.734

Gnomad4 NFE AF: 0.701

Gnomad4 OTH AF: 0.591

Alfa AF: 0.660 Hom.: 22369

Bravo AF: 0.579

Asia WGS AF: 0.568 AC: 1971 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2052910; hg19: chr2-141713645;