Variant chr1-115642000-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_138959.3(VANGL1):c.-224C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 151,386 control chromosomes in the GnomAD database, including 1,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1280 hom., cov: 30)

Exomes 𝑓: 0.24 ( 45 hom. )

Consequence

VANGL1
NM_138959.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.46

Variant links:

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]

VANGL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 1-115642000-C-A is Benign according to our data. Variant chr1-115642000-C-A is described in ClinVar as [Benign]. Clinvar id is 291998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VANGL1	NM_138959.3 linkuse as main transcript	c.-224C>A		5_prime_UTR_variant	1/8	ENST00000355485.7
VANGL1	NM_001172411.2 linkuse as main transcript	c.-224C>A		5_prime_UTR_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VANGL1	ENST00000355485.7 linkuse as main transcript	c.-224C>A		5_prime_UTR_variant	1/8	1	NM_138959.3	P3	Q8TAA9-1
VANGL1	ENST00000369510.8 linkuse as main transcript	c.-224C>A		5_prime_UTR_variant	1/8	1		A1	Q8TAA9-2

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17623

AN:

150272

Hom.:

1281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0726

Gnomad AMI

AF:

0.0831

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.0742

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.122

GnomAD4 exome

AF:

0.243

AC:

244

AN:

1006

Hom.:

Cov.:

AF XY:

0.214

AC XY:

120

AN XY:

560

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.227

Gnomad4 SAS exome

AF:

0.316

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0884

Gnomad4 OTH exome

AF:

0.300

GnomAD4 genome

AF:

0.117

AC:

17633

AN:

150380

Hom.:

1280

Cov.:

AF XY:

0.126

AC XY:

9272

AN XY:

73432

show subpopulations

Gnomad4 AFR

AF:

0.0725

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.112

Gnomad4 EAS

AF:

0.231

Gnomad4 SAS

AF:

0.330

Gnomad4 FIN

AF:

0.162

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.111

Hom.:

117

Bravo

AF:

0.111

Asia WGS

AF:

0.282

AC:

884

AN:

3140

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Sacral defect with anterior meningocele

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Neural tube defect

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over