rs886063803

Variant names:

• chr9-2622069-C-G
• rs886063803
• NM_003383.5:c.-121C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-2622069-C-G
• chr9-2622069-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003383.5(VLDLR):​c.-121C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000123 in 814,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: VLDLR NM_003383.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).

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.-121C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_003374.3
	VLDLR	NM_003383.5	MANE Select	c.-121C>G		5_prime_UTR	Exon 1 of 19	NP_003374.3
	VLDLR	NM_001018056.3		c.-121C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	NP_001018066.1	P98155-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VLDLR	ENST00000382100.8	TSL:1 MANE Select	c.-121C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	ENSP00000371532.2	P98155-1
	VLDLR	ENST00000382100.8	TSL:1 MANE Select	c.-121C>G		5_prime_UTR	Exon 1 of 19	ENSP00000371532.2	P98155-1
	VLDLR-AS1	ENST00000453601.5	TSL:1	n.274+31G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000123 AC: 1 AN: 814114 Hom.: 0 Cov.: 11 AF XY: 0.00000243 AC XY: 1 AN XY: 411028

African (AFR) AF: 0.00 AC: 0 AN: 16726

American (AMR) AF: 0.00 AC: 0 AN: 19376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15610

East Asian (EAS) AF: 0.00 AC: 0 AN: 25658

South Asian (SAS) AF: 0.00 AC: 0 AN: 53468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3672

European-Non Finnish (NFE) AF: 0.00000163 AC: 1 AN: 614122

Other (OTH) AF: 0.00 AC: 0 AN: 37022

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		0.13
PromoterAI		-0.078	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs886063803; hg19: chr9-2622069;