rs4245855

Variant names:

• chr2-141391759-G-A
• rs4245855
• NM_018557.3:c.343+88637C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018557.3(LRP1B):​c.343+88637C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 152,008 control chromosomes in the GnomAD database, including 24,702 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 0.55 (24702 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.343+88637C>T		intron_variant	Intron 3 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.-48+88637C>T		intron_variant	Intron 3 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.454+88637C>T		intron_variant	Intron 3 of 76		XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.343+88637C>T		intron_variant	Intron 3 of 90	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000434794.1	c.206-409483C>T		intron_variant	Intron 2 of 13	2		ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83926 AN: 151890 Hom.: 24697 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.552 AC: 83960 AN: 152008 Hom.: 24702 Cov.: 32 AF XY: 0.549 AC XY: 40802 AN XY: 74312

African (AFR) AF: 0.362 AC: 14994 AN: 41442

American (AMR) AF: 0.532 AC: 8128 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2070 AN: 3468

East Asian (EAS) AF: 0.293 AC: 1510 AN: 5162

South Asian (SAS) AF: 0.544 AC: 2624 AN: 4822

European-Finnish (FIN) AF: 0.683 AC: 7217 AN: 10562

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45453 AN: 67974

Other (OTH) AF: 0.565 AC: 1191 AN: 2108

Alfa AF: 0.621 Hom.: 123387

Bravo AF: 0.528

Asia WGS AF: 0.440 AC: 1529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.084
DANN	Benign	0.45
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4245855; hg19: chr2-142149328;