Genetic Variant VLDLR:c.-27_-19dupGGCGGCGGC (chr9-2622146-A-ACGGCGGCGG) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_003383.5(VLDLR):c.-27_-19dupGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00019 ( 1 hom. )

Consequence

VLDLR
NM_003383.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.20

Publications

3 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000186 (28/150672) while in subpopulation SAS AF = 0.00168 (8/4774). AF 95% confidence interval is 0.000834. There are 0 homozygotes in GnomAd4. There are 14 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003383.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VLDLR	NM_003383.5	MANE Select	c.-27_-19dupGGCGGCGGC	5_prime_UTR	Exon 1 of 19	NP_003374.3
VLDLR	NM_001018056.3		c.-27_-19dupGGCGGCGGC	5_prime_UTR	Exon 1 of 18	NP_001018066.1	P98155-2
VLDLR	NM_001322225.2		c.-27_-19dupGGCGGCGGC	5_prime_UTR	Exon 1 of 18	NP_001309154.1	A0A7P0T897

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VLDLR	ENST00000382100.8	TSL:1 MANE Select	c.-27_-19dupGGCGGCGGC	5_prime_UTR	Exon 1 of 19	ENSP00000371532.2	P98155-1
VLDLR-AS1	ENST00000453601.5	TSL:1	n.219_227dupCCGCCGCCG	non_coding_transcript_exon	Exon 1 of 4
VLDLR	ENST00000947327.1		c.-27_-19dupGGCGGCGGC	5_prime_UTR	Exon 1 of 19	ENSP00000617386.1

Frequencies

GnomAD3 genomes

AF:

0.000186

AC:

AN:

150562

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000976

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00167

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000208

Gnomad OTH

AF:

0.000962

GnomAD4 exome

AF:

0.000191

AC:

237

AN:

1241690

Hom.:

Cov.:

AF XY:

0.000226

AC XY:

138

AN XY:

610456

show subpopulations

African (AFR)

AF:

0.0000389

AC:

AN:

25712

American (AMR)

AF:

0.00

AC:

AN:

24124

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20260

East Asian (EAS)

AF:

0.0000335

AC:

AN:

29848

South Asian (SAS)

AF:

0.00117

AC:

AN:

64836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30350

Middle Eastern (MID)

AF:

0.000196

AC:

AN:

5100

European-Non Finnish (NFE)

AF:

0.000144

AC:

142

AN:

989386

Other (OTH)

AF:

0.000307

AC:

AN:

52074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000186

AC:

AN:

150672

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

AN XY:

73550

show subpopulations

African (AFR)

AF:

0.0000973

AC:

AN:

41122

American (AMR)

AF:

0.00

AC:

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

4972

South Asian (SAS)

AF:

0.00168

AC:

AN:

4774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000208

AC:

AN:

67432

Other (OTH)

AF:

0.000952

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

675

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.2

Mutation Taster

=300/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGGCGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over