Variant 9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_003383.5(VLDLR):c.-21_-19dupGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.25 ( 5849 hom., cov: 0)

Exomes 𝑓: 0.29 ( 37238 hom. )

Consequence

VLDLR
NM_003383.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:4

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 9-2622146-A-ACGG is Benign according to our data. Variant chr9-2622146-A-ACGG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 287823.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=3, Likely_benign=1}.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VLDLR	NM_003383.5 link	c.-21_-19dupGGC		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.-21_-19dupGGC		5_prime_UTR_variant	Exon 1 of 19	1	NM_003383.5	ENSP00000371532.2		P98155-1

Frequencies

GnomAD3 genomes

AF:

0.255

AC:

38285

AN:

150414

Hom.:

5843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0966

Gnomad AMI

AF:

0.562

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.0532

Gnomad SAS

AF:

0.366

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.330

Gnomad OTH

AF:

0.256

GnomAD3 exomes

AF:

0.302

AC:

15122

AN:

50120

Hom.:

1713

AF XY:

0.309

AC XY:

8680

AN XY:

28098

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.279

Gnomad ASJ exome

AF:

0.368

Gnomad EAS exome

AF:

0.0615

Gnomad SAS exome

AF:

0.372

Gnomad FIN exome

AF:

0.391

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.283

GnomAD4 exome

AF:

0.293

AC:

361375

AN:

1234812

Hom.:

37238

Cov.:

AF XY:

0.296

AC XY:

179468

AN XY:

607236

show subpopulations

Gnomad4 AFR exome

AF:

0.0877

Gnomad4 AMR exome

AF:

0.248

Gnomad4 ASJ exome

AF:

0.329

Gnomad4 EAS exome

AF:

0.0443

Gnomad4 SAS exome

AF:

0.342

Gnomad4 FIN exome

AF:

0.346

Gnomad4 NFE exome

AF:

0.302

Gnomad4 OTH exome

AF:

0.280

GnomAD4 genome

AF:

0.254

AC:

38305

AN:

150524

Hom.:

5849

Cov.:

AF XY:

0.256

AC XY:

18827

AN XY:

73460

show subpopulations

Gnomad4 AFR

AF:

0.0964

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.368

Gnomad4 EAS

AF:

0.0533

Gnomad4 SAS

AF:

0.366

Gnomad4 FIN

AF:

0.391

Gnomad4 NFE

AF:

0.330

Gnomad4 OTH

AF:

0.256

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	May 19, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 14, 2016	- -

Congenital cerebellar hypoplasia

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over