rs143196463

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_138959.3(VANGL1):c.274A>G(p.Ile92Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,614,208 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 3 hom. )

Consequence

VANGL1
NM_138959.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 0.891

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

neural tube defects, susceptibility to
Inheritance: AD Classification: LIMITED Submitted by: G2P

VANGL1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_138959.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009534031).

BP6

Variant 1-115663730-A-G is Benign according to our data. Variant chr1-115663730-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 445589.

BS2

High AC in GnomAd4 at 125 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138959.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VANGL1	NM_138959.3	MANE Select	c.274A>G	p.Ile92Val	missense	Exon 4 of 8	NP_620409.1	Q8TAA9-1
VANGL1	NM_001172412.2		c.274A>G	p.Ile92Val	missense	Exon 4 of 8	NP_001165883.1	Q8TAA9-1
VANGL1	NM_001172411.2		c.268A>G	p.Ile90Val	missense	Exon 4 of 8	NP_001165882.1	Q8TAA9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VANGL1	ENST00000355485.7	TSL:1 MANE Select	c.274A>G	p.Ile92Val	missense	Exon 4 of 8	ENSP00000347672.2	Q8TAA9-1
VANGL1	ENST00000310260.7	TSL:1	c.274A>G	p.Ile92Val	missense	Exon 4 of 8	ENSP00000310800.3	Q8TAA9-1
VANGL1	ENST00000369509.1	TSL:1	c.274A>G	p.Ile92Val	missense	Exon 3 of 7	ENSP00000358522.1	Q8TAA9-1

Frequencies

GnomAD3 genomes

AF:

0.000821

AC:

125

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

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:

0.00129

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000891

AC:

224

AN:

251482

AF XY:

0.000868

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00240

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00132

AC:

1926

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

923

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33480

American (AMR)

AF:

0.00248

AC:

111

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00156

AC:

1739

AN:

1112012

Other (OTH)

AF:

0.00103

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

131

262

393

524

655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000821

AC:

125

AN:

152314

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41578

American (AMR)

AF:

0.00144

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00129

AC:

AN:

68016

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000908

Hom.:

Bravo

AF:

0.00114

EpiCase

AF:

0.00136

EpiControl

AF:

0.00166

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Neural tube defect (1)

not provided (1)

Sacral defect with anterior meningocele (1)

VANGL1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.048

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.013

MetaRNN

Benign

0.0095

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.81

PhyloP100

0.89

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.22

REVEL

Benign

0.19

Sift

Benign

0.75

Sift4G

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.046

gMVP

0.32

Mutation Taster

=79/21

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over