chr2-141147483-G-T

Variant names:

• chr2-141147483-G-T
• rs7583934
• NM_018557.3:c.1013+40938C>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.1013+40938C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 152,000 control chromosomes in the GnomAD database, including 35,134 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 0.68 (35134 hom., cov: 33)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.702 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.1013+40938C>A		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.1013+40938C>A		intron	N/A	ENSP00000374135.3
	LRP1B	ENST00000434794.1	TSL:2	c.206-165207C>A		intron	N/A	ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103023 AN: 151882 Hom.: 35106 Cov.: 33

Gnomad AFR AF: 0.660

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.692

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

GnomAD4 genome AF: 0.678 AC: 103100 AN: 152000 Hom.: 35134 Cov.: 33 AF XY: 0.672 AC XY: 49941 AN XY: 74290

African (AFR) AF: 0.660 AC: 27367 AN: 41446

American (AMR) AF: 0.673 AC: 10272 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 2533 AN: 3470

East Asian (EAS) AF: 0.545 AC: 2819 AN: 5168

South Asian (SAS) AF: 0.711 AC: 3427 AN: 4818

European-Finnish (FIN) AF: 0.587 AC: 6193 AN: 10546

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48084 AN: 67980

Other (OTH) AF: 0.696 AC: 1469 AN: 2112

Alfa AF: 0.695 Hom.: 10870

Bravo AF: 0.684

Asia WGS AF: 0.674 AC: 2340 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.42
PhyloP100		0.41
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: rs7583934; hg19: chr2-141905052;