chr2-141907495-T-C

Variant names:

• chr2-141907495-T-C
• rs10496907
• NM_018557.3:c.83-97094A>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.83-97094A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 151,836 control chromosomes in the GnomAD database, including 5,075 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 0.24 (5075 hom., cov: 32)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP1B	NM_018557.3	c.83-97094A>G		intron_variant	Intron 1 of 90	ENST00000389484.8	NP_061027.2
LRP1B	XM_017004341.2	c.-308-97094A>G		intron_variant	Intron 1 of 90		XP_016859830.1
LRP1B	XM_047444771.1	c.194-97094A>G		intron_variant	Intron 1 of 76		XP_047300727.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP1B	ENST00000389484.8	c.83-97094A>G		intron_variant	Intron 1 of 90	1	NM_018557.3	ENSP00000374135.3
LRP1B	ENST00000434794.1	c.83-97094A>G		intron_variant	Intron 1 of 13	2		ENSP00000413239.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36342 AN: 151718 Hom.: 5067 Cov.: 32

Gnomad AFR AF: 0.0948

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.240 AC: 36368 AN: 151836 Hom.: 5075 Cov.: 32 AF XY: 0.243 AC XY: 17995 AN XY: 74200

African (AFR) AF: 0.0949 AC: 3935 AN: 41482

American (AMR) AF: 0.237 AC: 3601 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 803 AN: 3468

East Asian (EAS) AF: 0.367 AC: 1882 AN: 5134

South Asian (SAS) AF: 0.304 AC: 1464 AN: 4814

European-Finnish (FIN) AF: 0.321 AC: 3381 AN: 10544

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20520 AN: 67870

Other (OTH) AF: 0.237 AC: 501 AN: 2114

Alfa AF: 0.278 Hom.: 23087

Bravo AF: 0.226

Asia WGS AF: 0.296 AC: 1028 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.60
PhyloP100		-0.54
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: rs10496907; hg19: chr2-142665064;