Genetic Variant VLDLR:c.-27_-19delGGCGGCGGC (chr9-2622146-ACGGCGGCGG-A) – ACMG Classification: Benign (-9 pts)

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: {Benign=4, Uncertain_significance=1}.

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.

9-2622146-ACGGCGGCGGCGG-ACGG

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