2-141470940-C-T

Position:

• chr2-141470940-C-T

Variant summary

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

The NM_018557.3(LRP1B):​c.343+9456G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,090 control chromosomes in the GnomAD database, including 37,201 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 0.69 (37201 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.71

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]

LOC124906079 (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 (EAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.343+9456G>A		intron_variant		ENST00000389484.8	NP_061027.2
LOC124906079	XR_007087248.1	n.58-97C>T		intron_variant, non_coding_transcript_variant
LRP1B	XM_017004341.2	c.-48+9456G>A		intron_variant			XP_016859830.1
LRP1B	XM_047444771.1	c.454+9456G>A		intron_variant			XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.343+9456G>A		intron_variant		1	NM_018557.3	ENSP00000374135	P1
LRP1B	ENST00000434794.1	c.205+339339G>A		intron_variant		2		ENSP00000413239

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104226 AN: 151974 Hom.: 37181 Cov.: 32

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.719

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

GnomAD4 genome AF: 0.686 AC: 104294 AN: 152090 Hom.: 37201 Cov.: 32 AF XY: 0.687 AC XY: 51128 AN XY: 74370

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.780

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.581

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.774

Gnomad4 OTH AF: 0.718

Alfa AF: 0.775 Hom.: 42691

Bravo AF: 0.680

Asia WGS AF: 0.665 AC: 2310 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	0.015
DANN	Benign	0.41

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: rs12472911; hg19: chr2-142228509;