9-2622278-G-T

Variant names:

• chr9-2622278-G-T
• rs2219143
• ENST00000453601.5:n.96C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The ENST00000453601.5(VLDLR-AS1):​n.96C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,327,336 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: VLDLR-AS1 ENST00000453601.5 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.36
• Publications: 0 publications found

Genes affected

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

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 Gene-Disease associations (from GenCC):

• cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• cerebellar ataxia, intellectual disability, and dysequilibrium

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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=-0.41).
• BP6: Variant 9-2622278-G-T is Benign according to our data. Variant chr9-2622278-G-T is described in CliVar as Likely_benign. Clinvar id is 3672699.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-2622278-G-T is described in CliVar as Likely_benign. Clinvar id is 3672699.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-2622278-G-T is described in CliVar as Likely_benign. Clinvar id is 3672699.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-2622278-G-T is described in CliVar as Likely_benign. Clinvar id is 3672699.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-2622278-G-T is described in CliVar as Likely_benign. Clinvar id is 3672699.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-2622278-G-T is described in CliVar as Likely_benign. Clinvar id is 3672699.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-2622278-G-T is described in CliVar as Likely_benign. Clinvar id is 3672699.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-2622278-G-T is described in CliVar as Likely_benign. Clinvar id is 3672699.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-2622278-G-T is described in CliVar as Likely_benign. Clinvar id is 3672699.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-2622278-G-T is described in CliVar as Likely_benign. Clinvar id is 3672699.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-2622278-G-T is described in CliVar as Likely_benign. Clinvar id is 3672699.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-2622278-G-T is described in CliVar as Likely_benign. Clinvar id is 3672699.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-2622278-G-T is described in CliVar as Likely_benign. Clinvar id is 3672699.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-2622278-G-T is described in CliVar as Likely_benign. Clinvar id is 3672699.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-2622278-G-T is described in CliVar as Likely_benign. Clinvar id is 3672699.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VLDLR	NM_003383.5	c.82+7G>T		splice_region_variant, intron_variant	Intron 1 of 18	ENST00000382100.8	NP_003374.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VLDLR	ENST00000382100.8	c.82+7G>T		splice_region_variant, intron_variant	Intron 1 of 18	1	NM_003383.5	ENSP00000371532.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000151 AC: 2 AN: 1327336 Hom.: 0 Cov.: 36 AF XY: 0.00000306 AC XY: 2 AN XY: 653428

African (AFR) AF: 0.00 AC: 0 AN: 26984

American (AMR) AF: 0.00 AC: 0 AN: 29080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23360

East Asian (EAS) AF: 0.00 AC: 0 AN: 29986

South Asian (SAS) AF: 0.00 AC: 0 AN: 72534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32820

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4314

European-Non Finnish (NFE) AF: 0.00000190 AC: 2 AN: 1052886

Other (OTH) AF: 0.00 AC: 0 AN: 55372

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.97
PhyloP100		2.4
PromoterAI		-0.059	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: rs2219143; hg19: chr9-2622278;