9-2621030-C-A

Variant names:

• chr9-2621030-C-A
• rs1454626
• ENST00000453601.5:n.274+1070G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000743013.1(VLDLR-AS1):​n.357G>T 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 0.659 in 152,072 control chromosomes in the GnomAD database, including 33,678 homozygotes. 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: 𝑓 0.66 (33678 hom., cov: 32)
• Consequence: VLDLR-AS1 ENST00000743013.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.578
• Publications: 10 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: G2P, Labcorp Genetics (formerly Invitae), ClinGen
• cerebellar ataxia, intellectual disability, and dysequilibrium

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000743013.1. 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-AS1	NR_015375.2		n.274+1070G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VLDLR-AS1	ENST00000453601.5	TSL:1	n.274+1070G>T		intron	N/A
	VLDLR-AS1	ENST00000743013.1		n.357G>T		non_coding_transcript_exon	Exon 1 of 1
	VLDLR-AS1	ENST00000416826.6	TSL:2	n.185+199G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100203 AN: 151952 Hom.: 33657 Cov.: 32

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.712

Gnomad OTH AF: 0.652

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.659 AC: 100254 AN: 152072 Hom.: 33678 Cov.: 32 AF XY: 0.660 AC XY: 49106 AN XY: 74352

African (AFR) AF: 0.529 AC: 21938 AN: 41458

American (AMR) AF: 0.732 AC: 11194 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2233 AN: 3464

East Asian (EAS) AF: 0.775 AC: 4004 AN: 5164

South Asian (SAS) AF: 0.575 AC: 2772 AN: 4824

European-Finnish (FIN) AF: 0.721 AC: 7619 AN: 10572

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.712 AC: 48377 AN: 67990

Other (OTH) AF: 0.653 AC: 1379 AN: 2112

Alfa AF: 0.690 Hom.: 75792

Bravo AF: 0.657

Asia WGS AF: 0.685 AC: 2384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.2
DANN	Benign	0.77
PhyloP100		0.58
PromoterAI		-0.013	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1454626;

hg19: chr9-2621030;