9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGGCGG

Variant names:

• chr9-2622146-A-ACGGCGGCGG
• rs71329437
• NM_003383.5:c.-27_-19dupGGCGGCGGC

Variant summary

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

The NM_003383.5(VLDLR):​c.-27_-19dupGGCGGCGGC 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 0.00019 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00019 (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 sas. gnomad4 allele frequency = 0.000186 (28/150672) while in subpopulation SAS AF= 0.00168 (8/4774). AF 95% confidence interval is 0.000834. There are 0 homozygotes in gnomad4. There are 14 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.-27_-19dupGGCGGCGGC		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.-27_-19dupGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 19	1	NM_003383.5	ENSP00000371532.2

Frequencies

GnomAD3 genomes AF: 0.000186 AC: 28 AN: 150562 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000976

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00167

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000208

Gnomad OTH AF: 0.000962

GnomAD4 exome AF: 0.000191 AC: 237 AN: 1241690 Hom.: 1 Cov.: 0 AF XY: 0.000226 AC XY: 138 AN XY: 610456

Gnomad4 AFR exome AF: 0.0000389

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000335

Gnomad4 SAS exome AF: 0.00117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000144

Gnomad4 OTH exome AF: 0.000307

GnomAD4 genome AF: 0.000186 AC: 28 AN: 150672 Hom.: 0 Cov.: 0 AF XY: 0.000190 AC XY: 14 AN XY: 73550

Gnomad4 AFR AF: 0.0000973

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00168

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000208

Gnomad4 OTH AF: 0.000952

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;