chr2-140596827-G-T

Position:

• chr2-140596827-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.7194+1804C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,002 control chromosomes in the GnomAD database, including 3,460 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 0.20 (3460 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.245

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP1B	NM_018557.3	c.7194+1804C>A		intron_variant		ENST00000389484.8
LRP1B	XM_017004341.2	c.6804+1804C>A		intron_variant
LRP1B	XM_017004342.1	c.2046+1804C>A		intron_variant
LRP1B	XM_047444771.1	c.7305+1804C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP1B	ENST00000389484.8	c.7194+1804C>A		intron_variant		1	NM_018557.3	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30349 AN: 151886 Hom.: 3457 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.200 AC: 30367 AN: 152002 Hom.: 3460 Cov.: 32 AF XY: 0.206 AC XY: 15318 AN XY: 74284

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.209

Alfa AF: 0.204 Hom.: 5165

Bravo AF: 0.191

Asia WGS AF: 0.359 AC: 1251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.0
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1372256; hg19: chr2-141354396;