rs71329437

Variant names:

• chr9-2622146-ACGGCGGCGGCGG-A
• rs71329437
• ENST00000453601.5:n.216_227delCCGCCGCCGCCG

Your query was ambiguous. Multiple possible variants found:

• chr9-2622146-ACGGCGGCGGCGG-A
• chr9-2622146-ACGGCGGCGGCGG-ACGG
• chr9-2622146-ACGGCGGCGGCGG-ACGGCGG
• chr9-2622146-ACGGCGGCGGCGG-ACGGCGGCGG
• chr9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGG
• chr9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGG
• chr9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGGCGG
• chr9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGGCGGCGG
• chr9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGGCGGCGGCGG
• chr9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGGCGGCGGCGGCGG

Variant summary

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

The ENST00000453601.5(VLDLR-AS1):​n.216_227delCCGCCGCCGCCG variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,388,866 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: VLDLR-AS1 ENST00000453601.5 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45
• 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.-30_-19delGGCGGCGGCGGC		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.-30_-19delGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 19	1	NM_003383.5	ENSP00000371532.2

Frequencies

GnomAD3 genomes AF: 0.0000863 AC: 13 AN: 150560 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000198

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: 0.0000593

Gnomad OTH AF: 0.000481

GnomAD2 exomes AF: 0.000379 AC: 19 AN: 50120 AF XY: 0.000427

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.000473

Gnomad ASJ exome AF: 0.000615

Gnomad EAS exome AF: 0.000618

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000222

Gnomad OTH exome AF: 0.00189

GnomAD4 exome AF: 0.000131 AC: 162 AN: 1238306 Hom.: 0 AF XY: 0.000154 AC XY: 94 AN XY: 608734

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

African (AFR) AF: 0.0000778 AC: 2 AN: 25698

American (AMR) AF: 0.000291 AC: 7 AN: 24022

Ashkenazi Jewish (ASJ) AF: 0.0000989 AC: 2 AN: 20222

East Asian (EAS) AF: 0.000202 AC: 6 AN: 29770

South Asian (SAS) AF: 0.000154 AC: 10 AN: 64726

European-Finnish (FIN) AF: 0.0000330 AC: 1 AN: 30288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5090

European-Non Finnish (NFE) AF: 0.000122 AC: 120 AN: 986526

Other (OTH) AF: 0.000269 AC: 14 AN: 51964

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000863 AC: 13 AN: 150560 Hom.: 0 Cov.: 0 AF XY: 0.0000545 AC XY: 4 AN XY: 73430

African (AFR) AF: 0.000122 AC: 5 AN: 41004

American (AMR) AF: 0.000198 AC: 3 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 4988

South Asian (SAS) AF: 0.00 AC: 0 AN: 4778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000593 AC: 4 AN: 67440

Other (OTH) AF: 0.000481 AC: 1 AN: 2078

Alfa AF: 0.000435 Hom.: 675

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital cerebellar hypoplasia Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5

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;