chr9-2622146-ACGGCGG-A

Variant names:

• chr9-2622146-ACGGCGG-A
• rs71329437
• NM_003383.5:c.-24_-19delGGCGGC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_003383.5(VLDLR):​c.-24_-19delGGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,392,208 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0012 (6 hom.)
• Consequence: VLDLR NM_003383.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B: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: Benign. The variant received -10 ACMG points.

• BP6: Variant 9-2622146-ACGGCGG-A is Benign according to our data. Variant chr9-2622146-ACGGCGG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 420696.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00159 (240/150670) while in subpopulation SAS AF = 0.0044 (21/4774). AF 95% confidence interval is 0.00326. There are 1 homozygotes in GnomAd4. There are 107 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

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.-24_-19delGGCGGC		5_prime_UTR	Exon 1 of 19	NP_003374.3
	VLDLR	NM_001018056.3		c.-24_-19delGGCGGC		5_prime_UTR	Exon 1 of 18	NP_001018066.1	P98155-2
	VLDLR	NM_001322225.2		c.-24_-19delGGCGGC		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.-24_-19delGGCGGC		5_prime_UTR	Exon 1 of 19	ENSP00000371532.2	P98155-1
	VLDLR-AS1	ENST00000453601.5	TSL:1	n.222_227delCCGCCG		non_coding_transcript_exon	Exon 1 of 4
	VLDLR	ENST00000947327.1		c.-24_-19delGGCGGC		5_prime_UTR	Exon 1 of 19	ENSP00000617386.1

Frequencies

GnomAD3 genomes AF: 0.00159 AC: 239 AN: 150560 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00408

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000601

Gnomad SAS AF: 0.00440

Gnomad FIN AF: 0.000384

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.00241

GnomAD2 exomes AF: 0.00160 AC: 80 AN: 50120 AF XY: 0.00171

Gnomad AFR exome AF: 0.00193

Gnomad AMR exome AF: 0.00189

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00216

Gnomad FIN exome AF: 0.000904

Gnomad NFE exome AF: 0.000554

Gnomad OTH exome AF: 0.00126

GnomAD4 exome AF: 0.00120 AC: 1496 AN: 1241538 Hom.: 6 AF XY: 0.00133 AC XY: 814 AN XY: 610370

African (AFR) AF: 0.00140 AC: 36 AN: 25700

American (AMR) AF: 0.00207 AC: 50 AN: 24120

Ashkenazi Jewish (ASJ) AF: 0.0000987 AC: 2 AN: 20256

East Asian (EAS) AF: 0.000804 AC: 24 AN: 29844

South Asian (SAS) AF: 0.00466 AC: 302 AN: 64822

European-Finnish (FIN) AF: 0.000231 AC: 7 AN: 30350

Middle Eastern (MID) AF: 0.00137 AC: 7 AN: 5100

European-Non Finnish (NFE) AF: 0.00101 AC: 1004 AN: 989284

Other (OTH) AF: 0.00123 AC: 64 AN: 52062

GnomAD4 genome AF: 0.00159 AC: 240 AN: 150670 Hom.: 1 Cov.: 0 AF XY: 0.00145 AC XY: 107 AN XY: 73548

African (AFR) AF: 0.00180 AC: 74 AN: 41122

American (AMR) AF: 0.00408 AC: 62 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3462

East Asian (EAS) AF: 0.000603 AC: 3 AN: 4972

South Asian (SAS) AF: 0.00440 AC: 21 AN: 4774

European-Finnish (FIN) AF: 0.000384 AC: 4 AN: 10408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00104 AC: 70 AN: 67432

Other (OTH) AF: 0.00238 AC: 5 AN: 2100

Alfa AF: 0.000145 Hom.: 675

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=300/0	polymorphism

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;