1-115659527-G-A

Position:

• chr1-115659527-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_138959.3(VANGL1):​c.72-114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,277,830 control chromosomes in the GnomAD database, including 10,842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1049 hom., cov: 31)
  • Exomes 𝑓: 0.11 (9793 hom.)
• Consequence: VANGL1 NM_138959.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.237

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=-0.89).
• BP6: Variant 1-115659527-G-A is Benign according to our data. Variant chr1-115659527-G-A is described in ClinVar as [Benign]. Clinvar id is 1290410.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VANGL1	NM_138959.3	c.72-114G>A		intron_variant		ENST00000355485.7
VANGL1	NM_001172411.2	c.72-114G>A		intron_variant
VANGL1	NM_001172412.2	c.72-114G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VANGL1	ENST00000355485.7	c.72-114G>A		intron_variant		1	NM_138959.3	P3
VANGL1	ENST00000310260.7	c.72-114G>A		intron_variant		1		P3
VANGL1	ENST00000369509.1	c.72-114G>A		intron_variant		1		P3
VANGL1	ENST00000369510.8	c.72-114G>A		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16281 AN: 151516 Hom.: 1052 Cov.: 31

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0804

Gnomad ASJ AF: 0.0883

Gnomad EAS AF: 0.0734

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.112 AC: 126408 AN: 1126198 Hom.: 9793 AF XY: 0.119 AC XY: 68503 AN XY: 574778

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.0749

Gnomad4 ASJ exome AF: 0.0879

Gnomad4 EAS exome AF: 0.0580

Gnomad4 SAS exome AF: 0.312

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.0993

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.107 AC: 16292 AN: 151632 Hom.: 1049 Cov.: 31 AF XY: 0.112 AC XY: 8298 AN XY: 74080

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.0803

Gnomad4 ASJ AF: 0.0883

Gnomad4 EAS AF: 0.0734

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.105

Alfa AF: 0.104 Hom.: 58

Asia WGS AF: 0.182 AC: 633 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.94
DANN	Benign	0.27

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: rs45562632; hg19: chr1-116202148; COSMIC: COSV59621768;