chr2-140234778-T-C

Variant names:

• chr2-140234778-T-C
• rs78797806
• NM_018557.3:c.13659+8A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BA1

The NM_018557.3(LRP1B):​c.13659+8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 772,822 control chromosomes in the GnomAD database, including 1,984 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.049 (307 hom., cov: 31)
  • Exomes 𝑓: 0.063 (1677 hom.)
• Consequence: LRP1B NM_018557.3 splice_region, intron
• Scores: Splicing: ADA: 0.005132
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.16
• 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]

ENSG00000277306 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 2-140234778-T-C is Benign according to our data. Variant chr2-140234778-T-C is described in ClinVar as Benign. ClinVar VariationId is 3056106.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0626 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.13659+8A>G		splice_region intron	N/A	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.13659+8A>G		splice_region intron	N/A	ENSP00000374135.3	Q9NZR2
	LRP1B	ENST00000437977.5	TSL:5	c.2254-1452A>G		intron	N/A	ENSP00000415052.1	H0Y7T7
	ENSG00000277306	ENST00000622722.1	TSL:6	n.146A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0488 AC: 7371 AN: 151062 Hom.: 309 Cov.: 31

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.0642

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.000588

Gnomad SAS AF: 0.0646

Gnomad FIN AF: 0.0342

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0642

Gnomad OTH AF: 0.0829

GnomAD2 exomes AF: 0.0573 AC: 14043 AN: 245198 AF XY: 0.0618

Gnomad AFR exome AF: 0.00848

Gnomad AMR exome AF: 0.0428

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.000221

Gnomad FIN exome AF: 0.0326

Gnomad NFE exome AF: 0.0667

Gnomad OTH exome AF: 0.0773

GnomAD4 exome AF: 0.0626 AC: 38895 AN: 621642 Hom.: 1677 Cov.: 0 AF XY: 0.0648 AC XY: 21979 AN XY: 339034

African (AFR) AF: 0.0126 AC: 217 AN: 17268

American (AMR) AF: 0.0450 AC: 1942 AN: 43126

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 3950 AN: 20640

East Asian (EAS) AF: 0.000112 AC: 4 AN: 35814

South Asian (SAS) AF: 0.0696 AC: 4821 AN: 69234

European-Finnish (FIN) AF: 0.0339 AC: 1792 AN: 52900

Middle Eastern (MID) AF: 0.189 AC: 771 AN: 4072

European-Non Finnish (NFE) AF: 0.0665 AC: 23003 AN: 346030

Other (OTH) AF: 0.0736 AC: 2395 AN: 32558

GnomAD4 genome AF: 0.0488 AC: 7373 AN: 151180 Hom.: 307 Cov.: 31 AF XY: 0.0491 AC XY: 3628 AN XY: 73868

African (AFR) AF: 0.0106 AC: 440 AN: 41378

American (AMR) AF: 0.0641 AC: 970 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 644 AN: 3444

East Asian (EAS) AF: 0.000589 AC: 3 AN: 5090

South Asian (SAS) AF: 0.0657 AC: 316 AN: 4812

European-Finnish (FIN) AF: 0.0342 AC: 363 AN: 10604

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0642 AC: 4331 AN: 67426

Other (OTH) AF: 0.0825 AC: 173 AN: 2096

Alfa AF: 0.0645 Hom.: 182

Bravo AF: 0.0498

Asia WGS AF: 0.0290 AC: 102 AN: 3478

EpiCase AF: 0.0838

EpiControl AF: 0.0843

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	-0.38
CADD	Benign	17
DANN	Benign	0.86
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0051
dbscSNV1_RF	Benign	0.038
SpliceAI score (max)		0.12		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: rs78797806; hg19: chr2-140992347; COSMIC: COSV67198596;