9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGGCGGCGGCGG

Variant names:

• chr9-2622146-A-ACGGCGGCGGCGGCGG
• rs71329437
• ENST00000453601.5:n.213_227dupCCGCCGCCGCCGCCG

Variant summary

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

The ENST00000453601.5(VLDLR-AS1):​n.213_227dupCCGCCGCCGCCGCCG variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000032 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VLDLR-AS1 ENST00000453601.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 3 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), G2P, PanelApp Australia
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VLDLR	NM_003383.5	c.-33_-19dupGGCGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 19	ENST00000382100.8	NP_003374.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VLDLR	ENST00000382100.8	c.-33_-19dupGGCGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 19	1	NM_003383.5	ENSP00000371532.2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000322 AC: 4 AN: 1241702 Hom.: 0 Cov.: 0 AF XY: 0.00000328 AC XY: 2 AN XY: 610460

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25712

American (AMR) AF: 0.00 AC: 0 AN: 24124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20260

East Asian (EAS) AF: 0.00 AC: 0 AN: 29848

South Asian (SAS) AF: 0.00 AC: 0 AN: 64838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5100

European-Non Finnish (NFE) AF: 0.00000404 AC: 4 AN: 989396

Other (OTH) AF: 0.00 AC: 0 AN: 52074

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00302578), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 675

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2

Splicing

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

Other links and lift over

dbSNP: rs71329437; hg19: chr9-2622146;