2-141807723-C-T

Variant names:

• chr2-141807723-C-T
• rs972485
• NM_018557.3:c.205+2556G>A

Variant summary

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

The NM_018557.3(LRP1B):​c.205+2556G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,032 control chromosomes in the GnomAD database, including 3,010 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 0.18 (3010 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.205+2556G>A		intron_variant	Intron 2 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.-186+2556G>A		intron_variant	Intron 2 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.316+2556G>A		intron_variant	Intron 2 of 76		XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.205+2556G>A		intron_variant	Intron 2 of 90	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000434794.1	c.205+2556G>A		intron_variant	Intron 2 of 13	2		ENSP00000413239.1
LRP1B	ENST00000486364.1	n.124-1969G>A		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27928 AN: 151914 Hom.: 3012 Cov.: 32

Gnomad AFR AF: 0.0933

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.184 AC: 27924 AN: 152032 Hom.: 3010 Cov.: 32 AF XY: 0.188 AC XY: 13999 AN XY: 74306

African (AFR) AF: 0.0931 AC: 3865 AN: 41508

American (AMR) AF: 0.194 AC: 2955 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1155 AN: 3464

East Asian (EAS) AF: 0.388 AC: 1996 AN: 5146

South Asian (SAS) AF: 0.338 AC: 1629 AN: 4818

European-Finnish (FIN) AF: 0.164 AC: 1742 AN: 10594

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.203 AC: 13762 AN: 67940

Other (OTH) AF: 0.210 AC: 442 AN: 2108

Alfa AF: 0.202 Hom.: 9152

Bravo AF: 0.181

Asia WGS AF: 0.292 AC: 1014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.93
DANN	Benign	0.73
PhyloP100		-0.51
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: rs972485; hg19: chr2-142565292;