2-140246960-A-T

Variant names:

• chr2-140246960-A-T
• rs2129483
• NM_018557.3:c.13324+126T>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018557.3(LRP1B):​c.13324+126T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.13324+126T>A		intron_variant	Intron 87 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.12934+126T>A		intron_variant	Intron 87 of 90		XP_016859830.1
LRP1B	XM_017004342.1	c.8176+126T>A		intron_variant	Intron 58 of 61		XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.13324+126T>A		intron_variant	Intron 87 of 90	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000437977.5	c.2017+126T>A		intron_variant	Intron 14 of 16	5		ENSP00000415052.1
LRP1B	ENST00000442974.1	c.631+126T>A		intron_variant	Intron 5 of 6	5		ENSP00000393859.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 481548 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 257100

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.11
DANN	Benign	0.42

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: rs2129483; hg19: chr2-141004529;