2-140234776-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_018557.3(LRP1B):c.13659+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000781 in 771,908 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00034 (1 hom.)
• Consequence: LRP1B NM_018557.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.803

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 2-140234776-C-A is Benign according to our data. Variant chr2-140234776-C-A is described in ClinVar as [Benign]. Clinvar id is 719459.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 396 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRP1B	NM_018557.3	c.13659+10G>T		intron_variant		ENST00000389484.8
LRP1B	XM_017004341.2	c.13269+10G>T		intron_variant
LRP1B	XM_017004342.1	c.8511+10G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRP1B	ENST00000389484.8	c.13659+10G>T		intron_variant		1	NM_018557.3	P1
	ENST00000622722.1	n.148G>T		non_coding_transcript_exon_variant	1/1
LRP1B	ENST00000437977.5	c.2256-1450G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00262 AC: 396 AN: 151060 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00895

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00146

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000445

Gnomad OTH AF: 0.000966

GnomAD3 exomes AF: 0.000695 AC: 170 AN: 244570 Hom.: 1 AF XY: 0.000536 AC XY: 71 AN XY: 132494

Gnomad AFR exome AF: 0.00931

Gnomad AMR exome AF: 0.000355

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000823

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000335 AC: 208 AN: 620730 Hom.: 1 Cov.: 0 AF XY: 0.000286 AC XY: 97 AN XY: 338584

Gnomad4 AFR exome AF: 0.00824

Gnomad4 AMR exome AF: 0.000559

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000579

Gnomad4 OTH exome AF: 0.000584

GnomAD4 genome AF: 0.00261 AC: 395 AN: 151178 Hom.: 2 Cov.: 31 AF XY: 0.00255 AC XY: 188 AN XY: 73832

Gnomad4 AFR AF: 0.00890

Gnomad4 AMR AF: 0.00146

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000445

Gnomad4 OTH AF: 0.000956

Alfa AF: 0.00159 Hom.: 0

Bravo AF: 0.00298

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 17, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Benign	12
Dann	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs137949946; hg19: chr2-140992345;