1-115641975-AGCG-AGCGGCGGCG

Variant names:

• chr1-115641975-A-AGCGGCG
• rs886045116
• NM_138959.3:c.-238_-233dupCGGCGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138959.3(VANGL1):​c.-238_-233dupCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 150,006 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 30)
• Consequence: VANGL1 NM_138959.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24

Genes affected

VANGL1 (HGNC:15512): (VANGL planar cell polarity protein 1) This gene encodes a member of the tretraspanin family. The encoded protein may be involved in mediating intestinal trefoil factor induced wound healing in the intestinal mucosa. Mutations in this gene are associated with neural tube defects. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VANGL1	NM_138959.3	c.-238_-233dupCGGCGG		5_prime_UTR_variant	Exon 1 of 8	ENST00000355485.7	NP_620409.1
VANGL1	NM_001172411.2	c.-238_-233dupCGGCGG		5_prime_UTR_variant	Exon 1 of 8		NP_001165882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VANGL1	ENST00000355485	c.-238_-233dupCGGCGG		5_prime_UTR_variant	Exon 1 of 8	1	NM_138959.3	ENSP00000347672.2
VANGL1	ENST00000369510	c.-238_-233dupCGGCGG		5_prime_UTR_variant	Exon 1 of 8	1		ENSP00000358523.3
VANGL1	ENST00000369510.8	c.-249_-248insGCGGCG		upstream_gene_variant		1		ENSP00000358523.3

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 149904 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000662

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150006 Hom.: 0 Cov.: 30 AF XY: 0.0000137 AC XY: 1 AN XY: 73198

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.0000661

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs886045116; hg19: chr1-116184596;