Variant chr9-2622134-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003383.5(VLDLR):c.-56C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 1,441,502 control chromosomes in the GnomAD database, including 95,885 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8164 hom., cov: 30)

Exomes 𝑓: 0.36 ( 87721 hom. )

Consequence

VLDLR
NM_003383.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.127

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 9-2622134-C-T is Benign according to our data. Variant chr9-2622134-C-T is described in ClinVar as [Benign]. Clinvar id is 366354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VLDLR	NM_003383.5 linkuse as main transcript	c.-56C>T		5_prime_UTR_variant	1/19	ENST00000382100.8
VLDLR-AS1	NR_015375.2 linkuse as main transcript	n.240G>A		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VLDLR	ENST00000382100.8 linkuse as main transcript	c.-56C>T		5_prime_UTR_variant	1/19	1	NM_003383.5		P98155-1
VLDLR-AS1	ENST00000657742.1 linkuse as main transcript	n.240G>A		non_coding_transcript_exon_variant	1/10

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

46792

AN:

147390

Hom.:

8166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.217

Gnomad AMR

AF:

0.409

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.424

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.392

Gnomad OTH

AF:

0.325

GnomAD4 exome

AF:

0.362

AC:

468011

AN:

1294016

Hom.:

87721

Cov.:

AF XY:

0.357

AC XY:

226931

AN XY:

636032

show subpopulations

Gnomad4 AFR exome

AF:

0.138

Gnomad4 AMR exome

AF:

0.397

Gnomad4 ASJ exome

AF:

0.271

Gnomad4 EAS exome

AF:

0.405

Gnomad4 SAS exome

AF:

0.225

Gnomad4 FIN exome

AF:

0.365

Gnomad4 NFE exome

AF:

0.378

Gnomad4 OTH exome

AF:

0.337

GnomAD4 genome

AF:

0.317

AC:

46805

AN:

147486

Hom.:

8164

Cov.:

AF XY:

0.318

AC XY:

22879

AN XY:

71926

show subpopulations

Gnomad4 AFR

AF:

0.149

Gnomad4 AMR

AF:

0.409

Gnomad4 ASJ

AF:

0.283

Gnomad4 EAS

AF:

0.424

Gnomad4 SAS

AF:

0.252

Gnomad4 FIN

AF:

0.369

Gnomad4 NFE

AF:

0.392

Gnomad4 OTH

AF:

0.328

Alfa

AF:

0.343

Hom.:

4759

Bravo

AF:

0.311

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Congenital cerebellar hypoplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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