chr1-115641985-G-A

Position:

• chr1-115641985-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_138959.3(VANGL1):​c.-239G>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 0.00782 in 151,844 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0079 (11 hom., cov: 30)
  • Exomes 𝑓: 0.0018 (0 hom.)
• Consequence: VANGL1 NM_138959.3 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.20

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 1-115641985-G-A is Benign according to our data. Variant chr1-115641985-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 874453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 1185 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VANGL1	NM_138959.3	c.-239G>A		5_prime_UTR_variant	1/8	ENST00000355485.7
VANGL1	NM_001172411.2	c.-239G>A		5_prime_UTR_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VANGL1	ENST00000355485.7	c.-239G>A		5_prime_UTR_variant	1/8	1	NM_138959.3	P3
VANGL1	ENST00000369510.8			upstream_gene_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.00788 AC: 1187 AN: 150640 Hom.: 12 Cov.: 30

Gnomad AFR AF: 0.00206

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00218

Gnomad ASJ AF: 0.00116

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00850

Gnomad FIN AF: 0.0365

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00951

Gnomad OTH AF: 0.00533

GnomAD4 exome AF: 0.00182 AC: 2 AN: 1096 Hom.: 0 Cov.: 0 AF XY: 0.00163 AC XY: 1 AN XY: 612

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00273

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00786 AC: 1185 AN: 150748 Hom.: 11 Cov.: 30 AF XY: 0.00898 AC XY: 661 AN XY: 73632

Gnomad4 AFR AF: 0.00205

Gnomad4 AMR AF: 0.00217

Gnomad4 ASJ AF: 0.00116

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00851

Gnomad4 FIN AF: 0.0365

Gnomad4 NFE AF: 0.00948

Gnomad4 OTH AF: 0.00528

Alfa AF: 0.00709 Hom.: 1

Bravo AF: 0.00529

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely 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

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Neural tube defect Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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: rs563855412; hg19: chr1-116184606;