Variant 9-2622146-ACGG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_003383.5(VLDLR):c.-21_-19del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,374,274 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0028 ( 2 hom. )

Consequence

VLDLR
NM_003383.5 5_prime_UTR

Scores

Not classified

Clinical Significance

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 9-2622146-ACGG-A is Benign according to our data. Variant chr9-2622146-ACGG-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 366355.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}. Variant chr9-2622146-ACGG-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00153 (230/150640) while in subpopulation AMR AF= 0.00289 (44/15202). AF 95% confidence interval is 0.00222. There are 0 homozygotes in gnomad4. There are 110 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VLDLR	NM_003383.5 linkuse as main transcript	c.-21_-19del		5_prime_UTR_variant	1/19	ENST00000382100.8	NP_003374.3
VLDLR-AS1	NR_015375.2 linkuse as main transcript	n.225_227del		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VLDLR	ENST00000382100.8 linkuse as main transcript	c.-21_-19del		5_prime_UTR_variant	1/19	1	NM_003383.5	ENSP00000371532		P98155-1
VLDLR-AS1	ENST00000657742.1 linkuse as main transcript	n.225_227del		non_coding_transcript_exon_variant	1/10

Frequencies

GnomAD3 genomes

AF:

0.00153

AC:

231

AN:

150530

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000293

Gnomad AMI

AF:

0.0210

Gnomad AMR

AF:

0.00296

Gnomad ASJ

AF:

0.00145

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000628

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00209

Gnomad OTH

AF:

0.00289

GnomAD3 exomes

AF:

0.00465

AC:

233

AN:

50120

Hom.:

AF XY:

0.00438

AC XY:

123

AN XY:

28098

show subpopulations

Gnomad AFR exome

AF:

0.0174

Gnomad AMR exome

AF:

0.00407

Gnomad ASJ exome

AF:

0.00645

Gnomad EAS exome

AF:

0.00958

Gnomad SAS exome

AF:

0.00290

Gnomad FIN exome

AF:

0.000452

Gnomad NFE exome

AF:

0.00410

Gnomad OTH exome

AF:

0.00505

GnomAD4 exome

AF:

0.00277

AC:

3392

AN:

1223634

Hom.:

AF XY:

0.00274

AC XY:

1645

AN XY:

601320

show subpopulations

Gnomad4 AFR exome

AF:

0.00406

Gnomad4 AMR exome

AF:

0.00370

Gnomad4 ASJ exome

AF:

0.00412

Gnomad4 EAS exome

AF:

0.00162

Gnomad4 SAS exome

AF:

0.00131

Gnomad4 FIN exome

AF:

0.000200

Gnomad4 NFE exome

AF:

0.00285

Gnomad4 OTH exome

AF:

0.00334

GnomAD4 genome

AF:

0.00153

AC:

230

AN:

150640

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

110

AN XY:

73538

show subpopulations

Gnomad4 AFR

AF:

0.000292

Gnomad4 AMR

AF:

0.00289

Gnomad4 ASJ

AF:

0.00145

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000629

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00209

Gnomad4 OTH

AF:

0.00286

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Congenital cerebellar hypoplasia

Uncertain:1

Uncertain significance, 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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