chr1-115659527-G-A

Variant names:

• chr1-115659527-G-A
• rs45562632
• NM_138959.3:c.72-114G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VANGL1	NM_138959.3	MANE Select	c.72-114G>A		intron	N/A	NP_620409.1	Q8TAA9-1
	VANGL1	NM_001172412.2		c.72-114G>A		intron	N/A	NP_001165883.1	Q8TAA9-1
	VANGL1	NM_001172411.2		c.72-114G>A		intron	N/A	NP_001165882.1	Q8TAA9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VANGL1	ENST00000355485.7	TSL:1 MANE Select	c.72-114G>A		intron	N/A	ENSP00000347672.2	Q8TAA9-1
	VANGL1	ENST00000310260.7	TSL:1	c.72-114G>A		intron	N/A	ENSP00000310800.3	Q8TAA9-1
	VANGL1	ENST00000369509.1	TSL:1	c.72-114G>A		intron	N/A	ENSP00000358522.1	Q8TAA9-1

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

African (AFR) AF: 0.109 AC: 2951 AN: 27102

American (AMR) AF: 0.0749 AC: 3285 AN: 43874

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 2075 AN: 23618

East Asian (EAS) AF: 0.0580 AC: 2188 AN: 37706

South Asian (SAS) AF: 0.312 AC: 24285 AN: 77810

European-Finnish (FIN) AF: 0.109 AC: 4449 AN: 40914

Middle Eastern (MID) AF: 0.0993 AC: 356 AN: 3584

European-Non Finnish (NFE) AF: 0.0993 AC: 81617 AN: 822330

Other (OTH) AF: 0.106 AC: 5202 AN: 49260

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

African (AFR) AF: 0.108 AC: 4461 AN: 41226

American (AMR) AF: 0.0803 AC: 1225 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0883 AC: 306 AN: 3464

East Asian (EAS) AF: 0.0734 AC: 377 AN: 5136

South Asian (SAS) AF: 0.322 AC: 1539 AN: 4784

European-Finnish (FIN) AF: 0.109 AC: 1153 AN: 10542

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6921 AN: 67932

Other (OTH) AF: 0.105 AC: 220 AN: 2092

Alfa AF: 0.104 Hom.: 69

Asia WGS AF: 0.182 AC: 633 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.94
DANN	Benign	0.27
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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