rs71329437

Positions:

• 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. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003383.5(VLDLR):​c.-30_-19delGGCGGCGGCGGC variant causes a 5 prime UTR 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. 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 NM_003383.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45

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]

VLDLR-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VLDLR	NM_003383.5	c.-30_-19delGGCGGCGGCGGC		5_prime_UTR_variant	1/19	ENST00000382100.8	NP_003374.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VLDLR	ENST00000382100	c.-30_-19delGGCGGCGGCGGC		5_prime_UTR_variant	1/19	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

GnomAD3 exomes AF: 0.000379 AC: 19 AN: 50120 Hom.: 0 AF XY: 0.000427 AC XY: 12 AN XY: 28098

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 SAS exome AF: 0.000103

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

Gnomad4 AFR exome AF: 0.0000778

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.0000989

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.000154

Gnomad4 FIN exome AF: 0.0000330

Gnomad4 NFE exome AF: 0.000122

Gnomad4 OTH exome AF: 0.000269

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

Gnomad4 AFR AF: 0.000122

Gnomad4 AMR AF: 0.000198

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000593

Gnomad4 OTH AF: 0.000481

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

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71329437; hg19: chr9-2622146;