rs6735489

Positions:

• chr2-140793781-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.5360-17543T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,718 control chromosomes in the GnomAD database, including 9,529 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 0.35 (9529 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.5360-17543T>G		intron_variant		ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.4970-17543T>G		intron_variant			XP_016859830.1
LRP1B	XM_017004342.1	c.212-17543T>G		intron_variant			XP_016859831.1
LRP1B	XM_047444771.1	c.5471-17543T>G		intron_variant			XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.5360-17543T>G		intron_variant		1	NM_018557.3	ENSP00000374135	P1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53122 AN: 151600 Hom.: 9506 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.351 AC: 53189 AN: 151718 Hom.: 9529 Cov.: 32 AF XY: 0.352 AC XY: 26069 AN XY: 74100

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.336

Alfa AF: 0.308 Hom.: 9693

Bravo AF: 0.356

Asia WGS AF: 0.377 AC: 1304 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.6
DANN	Benign	0.47

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: rs6735489; hg19: chr2-141551350;