1-115684037-A-C

Position:

chr1-115684037-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_138959.3(VANGL1):c.1040A>C(p.Glu347Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 1,614,124 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 57 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 55 hom. )

Consequence

VANGL1
NM_138959.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 8.94

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:

VANGL1 (HGNC:):

VANGL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009638548).

BP6

Variant 1-115684037-A-C is Benign according to our data. Variant chr1-115684037-A-C is described in ClinVar as [Benign]. Clinvar id is 292011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VANGL1	NM_138959.3 linkuse as main transcript	c.1040A>C	p.Glu347Ala	missense_variant	6/8	ENST00000355485.7	NP_620409.1	Q8TAA9-1A0A024R0E3
VANGL1	NM_001172412.2 linkuse as main transcript	c.1040A>C	p.Glu347Ala	missense_variant	6/8		NP_001165883.1	Q8TAA9-1A0A024R0E3
VANGL1	NM_001172411.2 linkuse as main transcript	c.1034A>C	p.Glu345Ala	missense_variant	6/8		NP_001165882.1	Q8TAA9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VANGL1	ENST00000355485.7 linkuse as main transcript	c.1040A>C	p.Glu347Ala	missense_variant	6/8	1	NM_138959.3	ENSP00000347672.2		Q8TAA9-1

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2357

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0545

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00451

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00398

AC:

1001

AN:

251492

Hom.:

AF XY:

0.00293

AC XY:

398

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0538

Gnomad AMR exome

AF:

0.00280

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00157

AC:

2292

AN:

1461802

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

979

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0562

Gnomad4 AMR exome

AF:

0.00318

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000423

Gnomad4 OTH exome

AF:

0.00333

GnomAD4 genome

AF:

0.0155

AC:

2364

AN:

152322

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1124

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0545

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00290

Hom.:

Bravo

AF:

0.0174

ESP6500AA

AF:

0.0490

AC:

216

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00460

AC:

559

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Neural tube defect

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. -

Sacral defect with anterior meningocele

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

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.77

D;.;D;D

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D;.;.

MetaRNN

Benign

0.0096

T;T;T;T

MetaSVM

Uncertain

0.56

MutationAssessor

Benign

1.8

L;.;L;L

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-5.7

D;D;D;D

REVEL

Pathogenic

0.72

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.89

P;P;P;P

Vest4

0.83

MVP

0.56

MPC

0.47

ClinPred

0.040

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.77

gMVP

0.70

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