chr2 141254732 . T C

Variant names:

• chr2-141254732-T-C
• rs373757
• NM_018557.3:c.344-91A>G

Variant summary

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

The NM_018557.3(LRP1B):​c.344-91A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 972,638 control chromosomes in the GnomAD database, including 24,812 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 0.21 (3532 hom., cov: 32)
  • Exomes 𝑓: 0.23 (21280 hom.)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018557.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	NM_018557.3	MANE Select	c.344-91A>G		intron	N/A	NP_061027.2	Q9NZR2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	ENST00000389484.8	TSL:1 MANE Select	c.344-91A>G		intron	N/A	ENSP00000374135.3	Q9NZR2
	LRP1B	ENST00000434794.1	TSL:2	c.206-272456A>G		intron	N/A	ENSP00000413239.1	E7ERG8

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32289 AN: 151892 Hom.: 3520 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.225 AC: 184800 AN: 820628 Hom.: 21280 AF XY: 0.226 AC XY: 93309 AN XY: 413292

African (AFR) AF: 0.202 AC: 3415 AN: 16904

American (AMR) AF: 0.202 AC: 2918 AN: 14448

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 3724 AN: 16688

East Asian (EAS) AF: 0.148 AC: 4171 AN: 28180

South Asian (SAS) AF: 0.263 AC: 12188 AN: 46344

European-Finnish (FIN) AF: 0.213 AC: 7665 AN: 35946

Middle Eastern (MID) AF: 0.208 AC: 554 AN: 2664

European-Non Finnish (NFE) AF: 0.228 AC: 141782 AN: 622232

Other (OTH) AF: 0.225 AC: 8383 AN: 37222

GnomAD4 genome AF: 0.213 AC: 32327 AN: 152010 Hom.: 3532 Cov.: 32 AF XY: 0.212 AC XY: 15780 AN XY: 74320

African (AFR) AF: 0.202 AC: 8380 AN: 41502

American (AMR) AF: 0.208 AC: 3177 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 743 AN: 3458

East Asian (EAS) AF: 0.191 AC: 992 AN: 5182

South Asian (SAS) AF: 0.254 AC: 1227 AN: 4822

European-Finnish (FIN) AF: 0.223 AC: 2357 AN: 10580

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14705 AN: 67888

Other (OTH) AF: 0.218 AC: 461 AN: 2112

Alfa AF: 0.219 Hom.: 1777

Bravo AF: 0.213

Asia WGS AF: 0.219 AC: 761 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.63
PhyloP100		-0.27
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: rs373757; hg19: chr2-142012301; COSMIC: COSV104431431;