9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGG

Variant names:

• chr9-2622146-A-ACGGCGG
• rs71329437
• NM_003383.5:c.-24_-19dupGGCGGC

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:49621): (VLDLR antisense RNA 1)

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 rank	MANE	Protein	UniProt
VLDLR	NM_003383.5	c.-24_-19dupGGCGGC		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	c.-24_-19dupGGCGGC		5_prime_UTR_variant	Exon 1 of 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;