chr2-140793781-A-C

Variant names:

• chr2-140793781-A-C
• rs6735489
• NM_018557.3:c.5360-17543T>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.5360-17543T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,718 control chromosomes in the GnomAD database, including 9,529 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 0.35 (9529 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	NM_018557.3	MANE Select	c.5360-17543T>G		intron	N/A	NP_061027.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRP1B	ENST00000389484.8	TSL:1 MANE Select	c.5360-17543T>G		intron	N/A	ENSP00000374135.3

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53122 AN: 151600 Hom.: 9506 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.351 AC: 53189 AN: 151718 Hom.: 9529 Cov.: 32 AF XY: 0.352 AC XY: 26069 AN XY: 74100

African (AFR) AF: 0.437 AC: 18068 AN: 41384

American (AMR) AF: 0.340 AC: 5177 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 899 AN: 3470

East Asian (EAS) AF: 0.410 AC: 2119 AN: 5164

South Asian (SAS) AF: 0.340 AC: 1637 AN: 4814

European-Finnish (FIN) AF: 0.362 AC: 3797 AN: 10498

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20553 AN: 67830

Other (OTH) AF: 0.336 AC: 711 AN: 2114

Alfa AF: 0.314 Hom.: 12698

Bravo AF: 0.356

Asia WGS AF: 0.377 AC: 1304 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.6
DANN	Benign	0.47
PhyloP100		1.2
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: rs6735489; hg19: chr2-141551350;