9-2621675-G-A

Position:

• chr9-2621675-G-A

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+425C>T 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 0.0106 in 151,932 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.011 (12 hom., cov: 32)
• Consequence: VLDLR-AS1 NR_015375.2 intron, non_coding_transcript
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.234

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=-0.67).
• BP6: Variant 9-2621675-G-A is Benign according to our data. Variant chr9-2621675-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1201678.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0106 (1614/151932) while in subpopulation NFE AF= 0.0167 (1134/67892). AF 95% confidence interval is 0.0159. There are 12 homozygotes in gnomad4. There are 741 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VLDLR-AS1	NR_015375.2	n.274+425C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VLDLR-AS1	ENST00000657742.1	n.274+425C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 1615 AN: 151828 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00244

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00584

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0106

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.00864

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

GnomAD4 genome AF: 0.0106 AC: 1614 AN: 151932 Hom.: 12 Cov.: 32 AF XY: 0.00998 AC XY: 741 AN XY: 74262

Gnomad4 AFR AF: 0.00243

Gnomad4 AMR AF: 0.00583

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.0161

Gnomad4 NFE AF: 0.0167

Gnomad4 OTH AF: 0.00855

Alfa AF: 0.0131 Hom.: 1

Bravo AF: 0.00980

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

Oct 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.97

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs113361299; hg19: chr9-2621675;