Genetic Variant VLDLR:c.-30_-19dupGGCGGCGGCGGC (chr9-2622146-A-ACGGCGGCGGCGG) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_003383.5(VLDLR):c.-30_-19dupGGCGGCGGCGGC 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 0.000093 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

VLDLR
NM_003383.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.20

Variant links:

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 links:

VLDLR-AS1 (HGNC:49621): (VLDLR antisense RNA 1)

VLDLR-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000128 (159/1241698) while in subpopulation SAS AF= 0.00074 (48/64838). AF 95% confidence interval is 0.000573. There are 1 homozygotes in gnomad4_exome. There are 84 alleles in male gnomad4_exome 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 link	c.-30_-19dupGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 19	ENST00000382100.8	NP_003374.3	P98155-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VLDLR	ENST00000382100 link	c.-30_-19dupGGCGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 19	1	NM_003383.5	ENSP00000371532.2		P98155-1

Frequencies

GnomAD3 genomes

AF:

0.0000930

AC:

AN:

150562

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000837

Gnomad FIN

AF:

0.000480

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000741

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000128

AC:

159

AN:

1241698

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

AN XY:

610460

show subpopulations

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:

0.000740

Gnomad4 FIN exome

AF:

0.000165

Gnomad4 NFE exome

AF:

0.0000950

Gnomad4 OTH exome

AF:

0.000192

GnomAD4 genome

AF:

0.0000929

AC:

AN:

150672

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

73550

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000838

Gnomad4 FIN

AF:

0.000480

Gnomad4 NFE

AF:

0.0000741

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGGCGGCGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over