1-115641985-G-A

Variant names:

• chr1-115641985-G-A
• rs563855412
• NM_138959.3:c.-239G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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=-0.44).
• BP6: Variant 1-115641985-G-A is Benign according to our data. Variant chr1-115641985-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 874453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 1185 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VANGL1	NM_138959.3	MANE Select	c.-239G>A		5_prime_UTR	Exon 1 of 8	NP_620409.1	Q8TAA9-1
	VANGL1	NM_001172411.2		c.-239G>A		5_prime_UTR	Exon 1 of 8	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.-239G>A		5_prime_UTR	Exon 1 of 8	ENSP00000347672.2	Q8TAA9-1
	VANGL1	ENST00000927747.1		c.-239G>A		5_prime_UTR	Exon 1 of 9	ENSP00000597806.1
	VANGL1	ENST00000879940.1		c.-239G>A		5_prime_UTR	Exon 1 of 8	ENSP00000549999.1

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

African (AFR) AF: 0.00 AC: 0 AN: 10

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 18

South Asian (SAS) AF: 0.00273 AC: 2 AN: 732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 304

Other (OTH) AF: 0.00 AC: 0 AN: 16

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

African (AFR) AF: 0.00205 AC: 85 AN: 41364

American (AMR) AF: 0.00217 AC: 33 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.00116 AC: 4 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5092

South Asian (SAS) AF: 0.00851 AC: 41 AN: 4818

European-Finnish (FIN) AF: 0.0365 AC: 370 AN: 10150

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00948 AC: 639 AN: 67414

Other (OTH) AF: 0.00528 AC: 11 AN: 2084

Alfa AF: 0.00423 Hom.: 1

Bravo AF: 0.00529

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Neural tube defect (1)
-	-	1	not provided (1)
-	-	1	Sacral defect with anterior meningocele (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Benign	0.94
PhyloP100		1.2
PromoterAI		-0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Mutation Taster		=297/3	polymorphism

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: rs563855412; hg19: chr1-116184606;