chr2-140482029-G-T

Position:

• chr2-140482029-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.9425+3314C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 151,968 control chromosomes in the GnomAD database, including 4,996 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 0.25 (4996 hom., cov: 31)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.692

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP1B	NM_018557.3	c.9425+3314C>A		intron_variant		ENST00000389484.8
LRP1B	XM_017004341.2	c.9035+3314C>A		intron_variant
LRP1B	XM_017004342.1	c.4277+3314C>A		intron_variant
LRP1B	XM_047444771.1	c.9536+3314C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP1B	ENST00000389484.8	c.9425+3314C>A		intron_variant		1	NM_018557.3	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37650 AN: 151850 Hom.: 4997 Cov.: 31

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.248 AC: 37669 AN: 151968 Hom.: 4996 Cov.: 31 AF XY: 0.246 AC XY: 18302 AN XY: 74256

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.295

Alfa AF: 0.262 Hom.: 7343

Bravo AF: 0.264

Asia WGS AF: 0.221 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.41
DANN	Benign	0.33

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: rs3923350; hg19: chr2-141239598;