9-2621884-T-TCCCTCCTCTCCCCTTGCCTCCCCTCCTCTCCCCATGCCTC

Variant names:

• chr9-2621884-T-TCCCTCCTCTCCCCTTGCCTCCCCTCCTCTCCCCATGCCTC
• rs539873248
• NM_003383.5:c.-277_-276insCCCCATGCCTCCCCTCCTCTCCCCTTGCCTCCCCTCCTCT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003383.5(VLDLR):​c.-277_-276insCCCCATGCCTCCCCTCCTCTCCCCTTGCCTCCCCTCCTCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000224 in 446,302 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: VLDLR NM_003383.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.-277_-276insCCCCATGCCTCCCCTCCTCTCCCCTTGCCTCCCCTCCTCT		5_prime_UTR	Exon 1 of 19	NP_003374.3
	VLDLR	NM_001018056.3		c.-277_-276insCCCCATGCCTCCCCTCCTCTCCCCTTGCCTCCCCTCCTCT		5_prime_UTR	Exon 1 of 18	NP_001018066.1	P98155-2
	VLDLR	NM_001322225.2		c.-277_-276insCCCCATGCCTCCCCTCCTCTCCCCTTGCCTCCCCTCCTCT		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.-277_-276insCCCCATGCCTCCCCTCCTCTCCCCTTGCCTCCCCTCCTCT		5_prime_UTR	Exon 1 of 19	ENSP00000371532.2	P98155-1
	VLDLR-AS1	ENST00000453601.5	TSL:1	n.274+215_274+216insGAGGCATGGGGAGAGGAGGGGAGGCAAGGGGAGAGGAGGG		intron	N/A
	VLDLR	ENST00000947327.1		c.-277_-276insCCCCATGCCTCCCCTCCTCTCCCCTTGCCTCCCCTCCTCT		5_prime_UTR	Exon 1 of 19	ENSP00000617386.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000224 AC: 1 AN: 446302 Hom.: 0 Cov.: 0 AF XY: 0.00000408 AC XY: 1 AN XY: 245118

African (AFR) AF: 0.00 AC: 0 AN: 12648

American (AMR) AF: 0.00 AC: 0 AN: 31060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16320

East Asian (EAS) AF: 0.00 AC: 0 AN: 22776

South Asian (SAS) AF: 0.00 AC: 0 AN: 60192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1918

European-Non Finnish (NFE) AF: 0.00000395 AC: 1 AN: 252852

Other (OTH) AF: 0.00 AC: 0 AN: 24076

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.21

Splicing

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

Other links and lift over

dbSNP: rs539873248; hg19: chr9-2621884;