chr2-140635392-G-A

Variant names:

• chr2-140635392-G-A
• rs549904
• NM_018557.3:c.6800-33753C>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.6800-33753C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0825 in 151,730 control chromosomes in the GnomAD database, including 669 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 0.082 (669 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.6800-33753C>T		intron_variant	Intron 41 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.6410-33753C>T		intron_variant	Intron 41 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.6911-33753C>T		intron_variant	Intron 41 of 76		XP_047300727.1
LRP1B	XM_017004342.1	c.1652-33753C>T		intron_variant	Intron 12 of 61		XP_016859831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.6800-33753C>T		intron_variant	Intron 41 of 90	1	NM_018557.3	ENSP00000374135.3

Frequencies

GnomAD3 genomes AF: 0.0823 AC: 12482 AN: 151610 Hom.: 664 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0370

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0680

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.0256

Gnomad NFE AF: 0.0423

Gnomad OTH AF: 0.0716

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

GnomAD4 genome AF: 0.0825 AC: 12516 AN: 151730 Hom.: 669 Cov.: 32 AF XY: 0.0852 AC XY: 6319 AN XY: 74154

African (AFR) AF: 0.134 AC: 5531 AN: 41404

American (AMR) AF: 0.117 AC: 1785 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.0370 AC: 128 AN: 3464

East Asian (EAS) AF: 0.178 AC: 920 AN: 5158

South Asian (SAS) AF: 0.0682 AC: 328 AN: 4808

European-Finnish (FIN) AF: 0.0677 AC: 712 AN: 10510

Middle Eastern (MID) AF: 0.0276 AC: 8 AN: 290

European-Non Finnish (NFE) AF: 0.0423 AC: 2869 AN: 67842

Other (OTH) AF: 0.0756 AC: 159 AN: 2104

Alfa AF: 0.0617 Hom.: 161

Bravo AF: 0.0912

Asia WGS AF: 0.149 AC: 515 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.079
DANN	Benign	0.21
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs549904; hg19: chr2-141392961;