9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGG

Position:

• chr9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_003383.5(VLDLR):​c.-24_-19dupGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00064 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00069 (1 hom.)
• Consequence: VLDLR NM_003383.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20

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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000637 (96/150670) while in subpopulation EAS AF= 0.00724 (36/4970). AF 95% confidence interval is 0.00538. There are 0 homozygotes in gnomad4. There are 50 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VLDLR	NM_003383.5	c.-24_-19dupGGCGGC		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.-24_-19dupGGCGGC		5_prime_UTR_variant	1/19	1	NM_003383.5	ENSP00000371532.2

Frequencies

GnomAD3 genomes AF: 0.000644 AC: 97 AN: 150560 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000593

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00742

Gnomad SAS AF: 0.00105

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000534

Gnomad OTH AF: 0.000481

GnomAD3 exomes AF: 0.00102 AC: 51 AN: 50120 Hom.: 0 AF XY: 0.000747 AC XY: 21 AN XY: 28098

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000757

Gnomad ASJ exome AF: 0.000307

Gnomad EAS exome AF: 0.00803

Gnomad SAS exome AF: 0.000828

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000443

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000689 AC: 856 AN: 1241622 Hom.: 1 Cov.: 0 AF XY: 0.000695 AC XY: 424 AN XY: 610426

Gnomad4 AFR exome AF: 0.000311

Gnomad4 AMR exome AF: 0.000995

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00767

Gnomad4 SAS exome AF: 0.00139

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000455

Gnomad4 OTH exome AF: 0.000749

GnomAD4 genome AF: 0.000637 AC: 96 AN: 150670 Hom.: 0 Cov.: 0 AF XY: 0.000680 AC XY: 50 AN XY: 73548

Gnomad4 AFR AF: 0.000170

Gnomad4 AMR AF: 0.000592

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00724

Gnomad4 SAS AF: 0.00105

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000534

Gnomad4 OTH AF: 0.000476

ClinVar

Not reported in ClinVar

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;