Variant 9-2622146-ACGGCGGCGGCGG-ACGG 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.-27_-19delGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,386,978 control chromosomes in the GnomAD database, including 94,983 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.33 ( 8761 hom., cov: 0)

Exomes 𝑓: 0.38 ( 86222 hom. )

Consequence

VLDLR
NM_003383.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 2.45

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-ACGGCGGCGG-A is Benign according to our data. Variant chr9-2622146-ACGGCGGCGG-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 290493.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=4}.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VLDLR	NM_003383.5 link	c.-27_-19delGGCGGCGGC		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.-27_-19delGGCGGCGGC		5_prime_UTR_variant	Exon 1 of 19	1	NM_003383.5	ENSP00000371532.2		P98155-1

Frequencies

GnomAD3 genomes

AF:

0.329

AC:

49501

AN:

150360

Hom.:

8751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.414

Gnomad ASJ

AF:

0.298

Gnomad EAS

AF:

0.420

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.360

Gnomad MID

AF:

0.340

Gnomad NFE

AF:

0.388

Gnomad OTH

AF:

0.331

GnomAD3 exomes

AF:

0.302

AC:

15135

AN:

50120

Hom.:

2295

AF XY:

0.293

AC XY:

8222

AN XY:

28098

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.359

Gnomad ASJ exome

AF:

0.204

Gnomad EAS exome

AF:

0.433

Gnomad SAS exome

AF:

0.181

Gnomad FIN exome

AF:

0.302

Gnomad NFE exome

AF:

0.334

Gnomad OTH exome

AF:

0.324

GnomAD4 exome

AF:

0.380

AC:

469971

AN:

1236508

Hom.:

86222

AF XY:

0.375

AC XY:

227489

AN XY:

606996

show subpopulations

Gnomad4 AFR exome

AF:

0.194

Gnomad4 AMR exome

AF:

0.397

Gnomad4 ASJ exome

AF:

0.299

Gnomad4 EAS exome

AF:

0.414

Gnomad4 SAS exome

AF:

0.235

Gnomad4 FIN exome

AF:

0.383

Gnomad4 NFE exome

AF:

0.396

Gnomad4 OTH exome

AF:

0.356

GnomAD4 genome

AF:

0.329

AC:

49548

AN:

150470

Hom.:

8761

Cov.:

AF XY:

0.330

AC XY:

24225

AN XY:

73448

show subpopulations

Gnomad4 AFR

AF:

0.198

Gnomad4 AMR

AF:

0.414

Gnomad4 ASJ

AF:

0.298

Gnomad4 EAS

AF:

0.420

Gnomad4 SAS

AF:

0.238

Gnomad4 FIN

AF:

0.360

Gnomad4 NFE

AF:

0.388

Gnomad4 OTH

AF:

0.333

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Congenital cerebellar hypoplasia

Uncertain:1Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: flagged submission

Collection Method: clinical testing

- -

Jun 01, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Aug 17, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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