rs71329437

Variant names:

• chr9-2622146-ACGGCGGCGGCGG-A
• rs71329437
• NM_003383.5:c.-30_-19delGGCGGCGGCGGC

Your query was ambiguous. Multiple possible variants found:

• chr9-2622146-ACGGCGGCGGCGG-A
• chr9-2622146-ACGGCGGCGGCGG-ACGG
• chr9-2622146-ACGGCGGCGGCGG-ACGGCGG
• chr9-2622146-ACGGCGGCGGCGG-ACGGCGGCGG
• chr9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGG
• chr9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGG
• chr9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGGCGG
• chr9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGGCGGCGG
• chr9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGGCGGCGGCGG
• chr9-2622146-ACGGCGGCGGCGG-ACGGCGGCGGCGGCGGCGGCGGCGGCGGCGG

Variant summary

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

The NM_003383.5(VLDLR):​c.-30_-19delGGCGGCGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,388,866 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000086 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: VLDLR NM_003383.5 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45
• Publications: 3 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.

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.-30_-19delGGCGGCGGCGGC		5_prime_UTR	Exon 1 of 19	NP_003374.3
	VLDLR	NM_001018056.3		c.-30_-19delGGCGGCGGCGGC		5_prime_UTR	Exon 1 of 18	NP_001018066.1	P98155-2
	VLDLR	NM_001322225.2		c.-30_-19delGGCGGCGGCGGC		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.-30_-19delGGCGGCGGCGGC		5_prime_UTR	Exon 1 of 19	ENSP00000371532.2	P98155-1
	VLDLR-AS1	ENST00000453601.5	TSL:1	n.216_227delCCGCCGCCGCCG		non_coding_transcript_exon	Exon 1 of 4
	VLDLR	ENST00000947327.1		c.-30_-19delGGCGGCGGCGGC		5_prime_UTR	Exon 1 of 19	ENSP00000617386.1

Frequencies

GnomAD3 genomes AF: 0.0000863 AC: 13 AN: 150560 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000198

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: 0.0000593

Gnomad OTH AF: 0.000481

GnomAD2 exomes AF: 0.000379 AC: 19 AN: 50120 AF XY: 0.000427

Gnomad AFR exome AF: 0.00129

Gnomad AMR exome AF: 0.000473

Gnomad ASJ exome AF: 0.000615

Gnomad EAS exome AF: 0.000618

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000222

Gnomad OTH exome AF: 0.00189

GnomAD4 exome AF: 0.000131 AC: 162 AN: 1238306 Hom.: 0 AF XY: 0.000154 AC XY: 94 AN XY: 608734

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000778 AC: 2 AN: 25698

American (AMR) AF: 0.000291 AC: 7 AN: 24022

Ashkenazi Jewish (ASJ) AF: 0.0000989 AC: 2 AN: 20222

East Asian (EAS) AF: 0.000202 AC: 6 AN: 29770

South Asian (SAS) AF: 0.000154 AC: 10 AN: 64726

European-Finnish (FIN) AF: 0.0000330 AC: 1 AN: 30288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5090

European-Non Finnish (NFE) AF: 0.000122 AC: 120 AN: 986526

Other (OTH) AF: 0.000269 AC: 14 AN: 51964

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000863 AC: 13 AN: 150560 Hom.: 0 Cov.: 0 AF XY: 0.0000545 AC XY: 4 AN XY: 73430

African (AFR) AF: 0.000122 AC: 5 AN: 41004

American (AMR) AF: 0.000198 AC: 3 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 4988

South Asian (SAS) AF: 0.00 AC: 0 AN: 4778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000593 AC: 4 AN: 67440

Other (OTH) AF: 0.000481 AC: 1 AN: 2078

Alfa AF: 0.000435 Hom.: 675

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Congenital cerebellar hypoplasia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5

Splicing

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

Other links and lift over

dbSNP: rs71329437; hg19: chr9-2622146;