9-2621560-A-G

Position:

• chr9-2621560-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NR_015375.2(VLDLR-AS1):​n.274+540T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.004 in 394,298 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0052 (19 hom.)
• Consequence: VLDLR-AS1 NR_015375.2 intron, non_coding_transcript
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.84

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 9-2621560-A-G is Benign according to our data. Variant chr9-2621560-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1201496.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00516 (1250/242242) while in subpopulation EAS AF= 0.0338 (749/22160). AF 95% confidence interval is 0.0318. There are 19 homozygotes in gnomad4_exome. There are 589 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VLDLR-AS1	NR_015375.2	n.274+540T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VLDLR-AS1	ENST00000657742.1	n.274+540T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00215 AC: 326 AN: 151948 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0111

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0172

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000765

Gnomad OTH AF: 0.00192

GnomAD4 exome AF: 0.00516 AC: 1250 AN: 242242 Hom.: 19 AF XY: 0.00478 AC XY: 589 AN XY: 123220

Gnomad4 AFR exome AF: 0.000297

Gnomad4 AMR exome AF: 0.00241

Gnomad4 ASJ exome AF: 0.00250

Gnomad4 EAS exome AF: 0.0338

Gnomad4 SAS exome AF: 0.00107

Gnomad4 FIN exome AF: 0.0157

Gnomad4 NFE exome AF: 0.000625

Gnomad4 OTH exome AF: 0.00219

GnomAD4 genome AF: 0.00214 AC: 326 AN: 152056 Hom.: 3 Cov.: 32 AF XY: 0.00278 AC XY: 207 AN XY: 74346

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.0111

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0172

Gnomad4 NFE AF: 0.000765

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00194 Hom.: 0

Bravo AF: 0.000956

Asia WGS AF: 0.00783 AC: 27 AN: 3464

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs530164662; hg19: chr9-2621560;