NM_018557.3:c.4939+3385A>G

Variant names:

• chr2-140846717-T-C
• rs10166257
• NM_018557.3:c.4939+3385A>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.4939+3385A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 151,788 control chromosomes in the GnomAD database, including 1,978 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 0.15 (1978 hom., cov: 31)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 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.4939+3385A>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.4939+3385A>G		intron	N/A	ENSP00000374135.3

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22064 AN: 151670 Hom.: 1965 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0838

Gnomad EAS AF: 0.00466

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.146 AC: 22113 AN: 151788 Hom.: 1978 Cov.: 31 AF XY: 0.146 AC XY: 10825 AN XY: 74166

African (AFR) AF: 0.249 AC: 10307 AN: 41358

American (AMR) AF: 0.122 AC: 1858 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0838 AC: 290 AN: 3462

East Asian (EAS) AF: 0.00467 AC: 24 AN: 5138

South Asian (SAS) AF: 0.116 AC: 558 AN: 4816

European-Finnish (FIN) AF: 0.157 AC: 1648 AN: 10498

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7043 AN: 67942

Other (OTH) AF: 0.119 AC: 251 AN: 2110

Alfa AF: 0.110 Hom.: 1761

Bravo AF: 0.145

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.085
DANN	Benign	0.65
PhyloP100		-1.5
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: rs10166257; hg19: chr2-141604286;