rs7852409

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr9-2621482-C-A
• chr9-2621482-C-G
• chr9-2621482-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000453601.5(VLDLR-AS1):​n.274+618G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VLDLR-AS1 ENST00000453601.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 8 publications found

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]

VLDLR Gene-Disease associations (from GenCC):

• cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
• cerebellar ataxia, intellectual disability, and dysequilibrium

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000453601.5. 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
	VLDLR-AS1	NR_015375.2		n.274+618G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VLDLR-AS1	ENST00000453601.5	TSL:1	n.274+618G>T		intron	N/A
	VLDLR	ENST00000382096.6	TSL:5	c.-71+179C>A		intron	N/A	ENSP00000371528.2	Q5VVF8
	VLDLR-AS1	ENST00000657742.1		n.274+618G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 246780 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 125394

African (AFR) AF: 0.00 AC: 0 AN: 7022

American (AMR) AF: 0.00 AC: 0 AN: 7352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9158

East Asian (EAS) AF: 0.00 AC: 0 AN: 22836

South Asian (SAS) AF: 0.00 AC: 0 AN: 2592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 159464

Other (OTH) AF: 0.00 AC: 0 AN: 16364

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	13
DANN	Benign	0.88
PhyloP100		-0.070
PromoterAI		-0.083	Neutral

Splicing

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

Other links and lift over

dbSNP: rs7852409; hg19: chr9-2621482;