9-2622142-G-C

Variant names:

• chr9-2622142-G-C
• rs1054805961
• NM_003383.5:c.-48G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003383.5(VLDLR):​c.-48G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000099 (0 hom., cov: 31)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: VLDLR NM_003383.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.57
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).

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.-48G>C		5_prime_UTR	Exon 1 of 19	NP_003374.3
	VLDLR	NM_001018056.3		c.-48G>C		5_prime_UTR	Exon 1 of 18	NP_001018066.1	P98155-2
	VLDLR	NM_001322225.2		c.-48G>C		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.-48G>C		5_prime_UTR	Exon 1 of 19	ENSP00000371532.2	P98155-1
	VLDLR-AS1	ENST00000453601.5	TSL:1	n.232C>G		non_coding_transcript_exon	Exon 1 of 4
	VLDLR	ENST00000947327.1		c.-48G>C		5_prime_UTR	Exon 1 of 19	ENSP00000617386.1

Frequencies

GnomAD3 genomes AF: 0.00000993 AC: 1 AN: 100674 Hom.: 0 Cov.: 31

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000263

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.70e-7 AC: 1 AN: 1298020 Hom.: 0 Cov.: 24 AF XY: 0.00000156 AC XY: 1 AN XY: 638996

African (AFR) AF: 0.00 AC: 0 AN: 27346

American (AMR) AF: 0.00 AC: 0 AN: 27228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21868

East Asian (EAS) AF: 0.00 AC: 0 AN: 31408

South Asian (SAS) AF: 0.00 AC: 0 AN: 69968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5312

European-Non Finnish (NFE) AF: 9.72e-7 AC: 1 AN: 1028458

Other (OTH) AF: 0.00 AC: 0 AN: 54466

GnomAD4 genome AF: 0.00000993 AC: 1 AN: 100674 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 48962

African (AFR) AF: 0.00 AC: 0 AN: 37004

American (AMR) AF: 0.00 AC: 0 AN: 9112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2372

East Asian (EAS) AF: 0.00 AC: 0 AN: 3794

South Asian (SAS) AF: 0.00 AC: 0 AN: 3054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000263 AC: 1 AN: 38058

Other (OTH) AF: 0.00 AC: 0 AN: 1380

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Benign	0.94
PhyloP100		1.6
PromoterAI		-0.024	Neutral

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: rs1054805961; hg19: chr9-2622142;