rs1449477

Positions:

• chr2-142070339-C-A
• chr2-142070339-C-G
• chr2-142070339-C-T

Variant summary

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

The NM_018557.3(LRP1B):​c.82+60309G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,516 control chromosomes in the GnomAD database, including 15,890 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 0.43 (15890 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224

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=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.82+60309G>T		intron_variant		ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.-309+38521G>T		intron_variant			XP_016859830.1
LRP1B	XM_047444771.1	c.193+60309G>T		intron_variant			XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.82+60309G>T		intron_variant		1	NM_018557.3	ENSP00000374135	P1
LRP1B	ENST00000434794.1	c.82+60309G>T		intron_variant		2		ENSP00000413239

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64791 AN: 151400 Hom.: 15881 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.428 AC: 64794 AN: 151516 Hom.: 15890 Cov.: 32 AF XY: 0.432 AC XY: 31991 AN XY: 74040

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.687

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.443

Alfa AF: 0.467 Hom.: 7342

Bravo AF: 0.422

Asia WGS AF: 0.473 AC: 1644 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.79

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: rs1449477; hg19: chr2-142827908;