1-115642053-C-T

Variant names:

• chr1-115642053-C-T
• rs886045117
• NM_138959.3:c.-171C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138959.3(VANGL1):​c.-171C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VANGL1	NM_138959.3	c.-171C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8	ENST00000355485.7	NP_620409.1
VANGL1	NM_138959.3	c.-171C>T		5_prime_UTR_variant	Exon 1 of 8	ENST00000355485.7	NP_620409.1
VANGL1	NM_001172411.2	c.-171C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8		NP_001165882.1
VANGL1	NM_001172411.2	c.-171C>T		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.-171C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8	1	NM_138959.3	ENSP00000347672.2
VANGL1	ENST00000369510	c.-171C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8	1		ENSP00000358523.3
VANGL1	ENST00000355485	c.-171C>T		5_prime_UTR_variant	Exon 1 of 8	1	NM_138959.3	ENSP00000347672.2
VANGL1	ENST00000369510	c.-171C>T		5_prime_UTR_variant	Exon 1 of 8	1		ENSP00000358523.3

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151052 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151052 Hom.: 0 Cov.: 30 AF XY: 0.0000136 AC XY: 1 AN XY: 73720

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Benign	0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs886045117; hg19: chr1-116184674;