NM_018557.3:c.13047G>A

Variant names:

• chr2-140274519-C-T
• rs1386356
• NM_018557.3:c.13047G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_018557.3(LRP1B):​c.13047G>A​(p.Thr4349Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,611,552 control chromosomes in the GnomAD database, including 348,491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.54 (24585 hom., cov: 32)
  • Exomes 𝑓: 0.66 (323906 hom.)
• Consequence: LRP1B NM_018557.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.288
• Publications: 18 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]

ENSG00000300471 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.106).
• BP6: Variant 2-140274519-C-T is Benign according to our data. Variant chr2-140274519-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060762.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.288 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 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.13047G>A	p.Thr4349Thr	synonymous	Exon 85 of 91	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.13047G>A	p.Thr4349Thr	synonymous	Exon 85 of 91	ENSP00000374135.3	Q9NZR2
	LRP1B	ENST00000437977.5	TSL:5	c.1740G>A	p.Thr580Thr	synonymous	Exon 12 of 17	ENSP00000415052.1	H0Y7T7
	LRP1B	ENST00000442974.1	TSL:5	c.240G>A	p.Thr80Thr	synonymous	Exon 2 of 7	ENSP00000393859.1	H7C0A8

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81215 AN: 151616 Hom.: 24588 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.554

GnomAD2 exomes AF: 0.608 AC: 152554 AN: 250726 AF XY: 0.615

Gnomad AFR exome AF: 0.232

Gnomad AMR exome AF: 0.534

Gnomad ASJ exome AF: 0.518

Gnomad EAS exome AF: 0.685

Gnomad FIN exome AF: 0.689

Gnomad NFE exome AF: 0.673

Gnomad OTH exome AF: 0.614

GnomAD4 exome AF: 0.660 AC: 963582 AN: 1459820 Hom.: 323906 Cov.: 42 AF XY: 0.659 AC XY: 478315 AN XY: 726262

African (AFR) AF: 0.223 AC: 7460 AN: 33382

American (AMR) AF: 0.537 AC: 23959 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 13690 AN: 26060

East Asian (EAS) AF: 0.669 AC: 26518 AN: 39654

South Asian (SAS) AF: 0.580 AC: 49996 AN: 86182

European-Finnish (FIN) AF: 0.681 AC: 36315 AN: 53358

Middle Eastern (MID) AF: 0.539 AC: 3106 AN: 5758

European-Non Finnish (NFE) AF: 0.689 AC: 764752 AN: 1110550

Other (OTH) AF: 0.627 AC: 37786 AN: 60292

GnomAD4 genome AF: 0.535 AC: 81230 AN: 151732 Hom.: 24585 Cov.: 32 AF XY: 0.537 AC XY: 39771 AN XY: 74130

African (AFR) AF: 0.238 AC: 9874 AN: 41408

American (AMR) AF: 0.536 AC: 8145 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 1855 AN: 3460

East Asian (EAS) AF: 0.674 AC: 3445 AN: 5112

South Asian (SAS) AF: 0.554 AC: 2667 AN: 4818

European-Finnish (FIN) AF: 0.702 AC: 7404 AN: 10548

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45872 AN: 67896

Other (OTH) AF: 0.547 AC: 1151 AN: 2106

Alfa AF: 0.559 Hom.: 20820

Bravo AF: 0.512

Asia WGS AF: 0.563 AC: 1954 AN: 3476

EpiCase AF: 0.663

EpiControl AF: 0.657

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	LRP1B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.8
DANN	Benign	0.61
PhyloP100		0.29
Mutation Taster		=98/2	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: rs1386356; hg19: chr2-141032088; COSMIC: COSV67186048;