rs3780181

Positions:

• chr9-2640759-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003383.5(VLDLR):​c.326-618A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,198 control chromosomes in the GnomAD database, including 1,279 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1279 hom., cov: 32)
• Consequence: VLDLR NM_003383.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.657

Genes affected

VLDLR (HGNC:12698): (very low density lipoprotein receptor) The low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. This gene encodes a lipoprotein receptor that is a member of the LDLR family and plays important roles in VLDL-triglyceride metabolism and the reelin signaling pathway. Mutations in this gene cause VLDLR-associated cerebellar hypoplasia. Alternative splicing generates multiple transcript variants encoding distinct isoforms for this gene. [provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-2640759-A-G is Benign according to our data. Variant chr9-2640759-A-G is described in ClinVar as [Benign]. Clinvar id is 1181633.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VLDLR	NM_003383.5	c.326-618A>G		intron_variant		ENST00000382100.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VLDLR	ENST00000382100.8	c.326-618A>G		intron_variant		1	NM_003383.5

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17157 AN: 152080 Hom.: 1278 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0592

Gnomad FIN AF: 0.0473

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0694

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.113 AC: 17177 AN: 152198 Hom.: 1279 Cov.: 32 AF XY: 0.111 AC XY: 8272 AN XY: 74426

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.0592

Gnomad4 FIN AF: 0.0473

Gnomad4 NFE AF: 0.0693

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0748 Hom.: 1127

Bravo AF: 0.121

Asia WGS AF: 0.0980 AC: 342 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

GeneDx

Aug 23, 2019

This variant is associated with the following publications: (PMID: 30445632) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.73
DANN	Benign	0.73

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: rs3780181; hg19: chr9-2640759;