rs12379259

Variant names:

• chr9-2622121-A-G
• rs12379259
• NM_003383.5:c.-69A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-2622121-A-G
• chr9-2622121-A-T
• chr9-2622121-A-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003383.5(VLDLR):​c.-69A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,400,890 control chromosomes in the GnomAD database, including 419,861 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (50035 hom., cov: 27)
  • Exomes 𝑓: 0.77 (369826 hom.)
• Consequence: VLDLR NM_003383.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.10
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 9-2622121-A-G is Benign according to our data. Variant chr9-2622121-A-G is described in ClinVar as Benign. ClinVar VariationId is 366352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

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.-69A>G		5_prime_UTR	Exon 1 of 19	NP_003374.3
	VLDLR	NM_001018056.3		c.-69A>G		5_prime_UTR	Exon 1 of 18	NP_001018066.1	P98155-2
	VLDLR	NM_001322225.2		c.-69A>G		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.-69A>G		5_prime_UTR	Exon 1 of 19	ENSP00000371532.2	P98155-1
	VLDLR-AS1	ENST00000453601.5	TSL:1	n.253T>C		non_coding_transcript_exon	Exon 1 of 4
	VLDLR	ENST00000382096.6	TSL:5	c.-69A>G		splice_region	Exon 2 of 4	ENSP00000371528.2	Q5VVF8

Frequencies

GnomAD3 genomes AF: 0.811 AC: 122410 AN: 150928 Hom.: 49978 Cov.: 27

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.827

Gnomad MID AF: 0.692

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.794

GnomAD4 exome AF: 0.767 AC: 958558 AN: 1249854 Hom.: 369826 Cov.: 18 AF XY: 0.761 AC XY: 468656 AN XY: 615814

African (AFR) AF: 0.890 AC: 23228 AN: 26094

American (AMR) AF: 0.851 AC: 21904 AN: 25742

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 14084 AN: 20898

East Asian (EAS) AF: 0.822 AC: 25136 AN: 30588

South Asian (SAS) AF: 0.596 AC: 40259 AN: 67582

European-Finnish (FIN) AF: 0.833 AC: 26240 AN: 31518

Middle Eastern (MID) AF: 0.701 AC: 3622 AN: 5166

European-Non Finnish (NFE) AF: 0.772 AC: 764122 AN: 989762

Other (OTH) AF: 0.761 AC: 39963 AN: 52504

GnomAD4 genome AF: 0.811 AC: 122526 AN: 151036 Hom.: 50035 Cov.: 27 AF XY: 0.811 AC XY: 59716 AN XY: 73654

African (AFR) AF: 0.890 AC: 36763 AN: 41322

American (AMR) AF: 0.848 AC: 12911 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2329 AN: 3460

East Asian (EAS) AF: 0.809 AC: 3985 AN: 4928

South Asian (SAS) AF: 0.611 AC: 2897 AN: 4742

European-Finnish (FIN) AF: 0.827 AC: 8644 AN: 10446

Middle Eastern (MID) AF: 0.702 AC: 205 AN: 292

European-Non Finnish (NFE) AF: 0.777 AC: 52552 AN: 67610

Other (OTH) AF: 0.794 AC: 1671 AN: 2104

Alfa AF: 0.785 Hom.: 13059

Bravo AF: 0.818

Asia WGS AF: 0.748 AC: 2590 AN: 3462

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 (1)
-	-	1	Congenital cerebellar hypoplasia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	19
DANN	Benign	0.88
PhyloP100		2.1
PromoterAI		0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12379259; hg19: chr9-2622121; COSMIC: COSV66073714; COSMIC: COSV66073714;