9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGGCGGCGG

Variant names:

• chr9-2622146-A-ACGGCGGCGGCGG
• rs71329437
• NM_003383.5:c.-30_-19dupGGCGGCGGCGGC

Variant summary

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

The NM_003383.5(VLDLR):​c.-30_-19dupGGCGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000093 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: VLDLR NM_003383.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 3 publications found

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-AS1 (HGNC:49621): (VLDLR antisense RNA 1)

ACMG classification

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

• BS1: Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.000128 (159/1241698) while in subpopulation SAS AF = 0.00074 (48/64838). AF 95% confidence interval is 0.000573. There are 1 homozygotes in GnomAdExome4. There are 84 alleles in the male GnomAdExome4 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VLDLR	NM_003383.5	MANE Select	c.-30_-19dupGGCGGCGGCGGC		5_prime_UTR	Exon 1 of 19	NP_003374.3
	VLDLR	NM_001018056.3		c.-30_-19dupGGCGGCGGCGGC		5_prime_UTR	Exon 1 of 18	NP_001018066.1	P98155-2
	VLDLR	NM_001322225.2		c.-30_-19dupGGCGGCGGCGGC		5_prime_UTR	Exon 1 of 18	NP_001309154.1	A0A7P0T897

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VLDLR	ENST00000382100.8	TSL:1 MANE Select	c.-30_-19dupGGCGGCGGCGGC		5_prime_UTR	Exon 1 of 19	ENSP00000371532.2	P98155-1
	VLDLR-AS1	ENST00000453601.5	TSL:1	n.216_227dupCCGCCGCCGCCG		non_coding_transcript_exon	Exon 1 of 4
	VLDLR	ENST00000947327.1		c.-30_-19dupGGCGGCGGCGGC		5_prime_UTR	Exon 1 of 19	ENSP00000617386.1

Frequencies

GnomAD3 genomes AF: 0.0000930 AC: 14 AN: 150562 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000837

Gnomad FIN AF: 0.000480

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000741

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000128 AC: 159 AN: 1241698 Hom.: 1 Cov.: 0 AF XY: 0.000138 AC XY: 84 AN XY: 610460

African (AFR) AF: 0.0000389 AC: 1 AN: 25712

American (AMR) AF: 0.00 AC: 0 AN: 24124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20260

East Asian (EAS) AF: 0.0000335 AC: 1 AN: 29848

South Asian (SAS) AF: 0.000740 AC: 48 AN: 64838

European-Finnish (FIN) AF: 0.000165 AC: 5 AN: 30350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5100

European-Non Finnish (NFE) AF: 0.0000950 AC: 94 AN: 989394

Other (OTH) AF: 0.000192 AC: 10 AN: 52072

GnomAD4 genome AF: 0.0000929 AC: 14 AN: 150672 Hom.: 0 Cov.: 0 AF XY: 0.000122 AC XY: 9 AN XY: 73550

African (AFR) AF: 0.00 AC: 0 AN: 41122

American (AMR) AF: 0.00 AC: 0 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 4972

South Asian (SAS) AF: 0.000838 AC: 4 AN: 4774

European-Finnish (FIN) AF: 0.000480 AC: 5 AN: 10410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000741 AC: 5 AN: 67432

Other (OTH) AF: 0.00 AC: 0 AN: 2100

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

Splicing

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

Other links and lift over

dbSNP: rs71329437; hg19: chr9-2622146;