1-115698135-T-TC

Position:

• chr1-115698135-T-TC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_138959.3(VANGL1):​c.*6763dup variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,030 control chromosomes in the GnomAD database, including 2,241 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2241 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: VANGL1 NM_138959.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -0.494

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 1-115698135-T-TC is Benign according to our data. Variant chr1-115698135-T-TC is described in ClinVar as [Likely_benign]. Clinvar id is 292113.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VANGL1	NM_138959.3	c.*6763dup		3_prime_UTR_variant	8/8	ENST00000355485.7	NP_620409.1
VANGL1	NM_001172411.2	c.*6763dup		3_prime_UTR_variant	8/8		NP_001165882.1
VANGL1	NM_001172412.2	c.*6763dup		3_prime_UTR_variant	8/8		NP_001165883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VANGL1	ENST00000355485.7	c.*6763dup		3_prime_UTR_variant	8/8	1	NM_138959.3	ENSP00000347672	P3
VANGL1	ENST00000369510.8	c.*6763dup		3_prime_UTR_variant	8/8	1		ENSP00000358523	A1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25125 AN: 151910 Hom.: 2230 Cov.: 30

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.169

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.165 AC: 25158 AN: 152030 Hom.: 2241 Cov.: 30 AF XY: 0.168 AC XY: 12456 AN XY: 74304

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.167

Bravo AF: 0.166

Asia WGS AF: 0.143 AC: 497 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

Catecholaminergic polymorphic ventricular tachycardia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Caudal regression sequence Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Neural tube defect Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs5777244; hg19: chr1-116240756;