ENST00000453601.5:n.274+618G>C

Variant names:

• chr9-2621482-C-G
• rs7852409
• ENST00000453601.5:n.274+618G>C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000453601.5(VLDLR-AS1):​n.274+618G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 398,658 control chromosomes in the GnomAD database, including 106,004 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.68 (36009 hom., cov: 33)
  • Exomes 𝑓: 0.75 (69995 hom.)
• Consequence: VLDLR-AS1 ENST00000453601.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0700

Genes affected

VLDLR-AS1 (HGNC:49621): (VLDLR antisense RNA 1)

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 9-2621482-C-G is Benign according to our data. Variant chr9-2621482-C-G is described in ClinVar as [Benign]. Clinvar id is 667580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VLDLR-AS1	NR_015375.2	n.274+618G>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VLDLR-AS1	ENST00000453601.5	n.274+618G>C		intron_variant	Intron 1 of 3	1
VLDLR	ENST00000382096.6	c.-71+179C>G		intron_variant	Intron 1 of 3	5		ENSP00000371528.2
VLDLR-AS1	ENST00000657742.1	n.274+618G>C		intron_variant	Intron 1 of 9

Frequencies

GnomAD3 genomes AF: 0.677 AC: 102868 AN: 151938 Hom.: 35998 Cov.: 33

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.695

GnomAD4 exome AF: 0.752 AC: 185421 AN: 246606 Hom.: 69995 AF XY: 0.754 AC XY: 94505 AN XY: 125310

Gnomad4 AFR exome AF: 0.513

Gnomad4 AMR exome AF: 0.653

Gnomad4 ASJ exome AF: 0.746

Gnomad4 EAS exome AF: 0.829

Gnomad4 SAS exome AF: 0.745

Gnomad4 FIN exome AF: 0.722

Gnomad4 NFE exome AF: 0.762

Gnomad4 OTH exome AF: 0.735

GnomAD4 genome AF: 0.677 AC: 102923 AN: 152052 Hom.: 36009 Cov.: 33 AF XY: 0.678 AC XY: 50381 AN XY: 74328

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.729

Gnomad4 EAS AF: 0.840

Gnomad4 SAS AF: 0.753

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.762

Gnomad4 OTH AF: 0.700

Alfa AF: 0.621 Hom.: 1942

Bravo AF: 0.665

Asia WGS AF: 0.776 AC: 2697 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	14
DANN	Benign	0.86

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7852409; hg19: chr9-2621482;