rs10190730

chr2-141627229-T-C

Variant summary

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

The NM_018557.3(LRP1B):c.206-146696A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,284 control chromosomes in the GnomAD database, including 1,422 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 0.13 (1422 hom., cov: 33)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119

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]

LOC107985779 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP1B	NM_018557.3	c.206-146696A>G		intron_variant		ENST00000389484.8
LOC107985779	XR_007087247.1	n.154+15628T>C		intron_variant, non_coding_transcript_variant
LRP1B	XM_017004341.2	c.-185-146696A>G		intron_variant
LRP1B	XM_047444771.1	c.317-146696A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP1B	ENST00000389484.8	c.206-146696A>G		intron_variant		1	NM_018557.3	P1
LRP1B	ENST00000434794.1	c.205+183050A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19605 AN: 152166 Hom.: 1423 Cov.: 33

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0794

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.129 AC: 19621 AN: 152284 Hom.: 1422 Cov.: 33 AF XY: 0.130 AC XY: 9662 AN XY: 74464

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.0794

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.122

Alfa AF: 0.106 Hom.: 793

Bravo AF: 0.128

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.0
Dann	Benign	0.61

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: rs10190730; hg19: chr2-142384798;