rs17500488

Variant names:

• chr1-115669142-T-C
• rs17500488
• NM_138959.3:c.812+4874T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138959.3(VANGL1):​c.812+4874T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0831 in 152,190 control chromosomes in the GnomAD database, including 542 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.083 (542 hom., cov: 33)
• Consequence: VANGL1 NM_138959.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VANGL1	NM_138959.3	c.812+4874T>C		intron_variant	Intron 4 of 7	ENST00000355485.7	NP_620409.1
VANGL1	NM_001172412.2	c.812+4874T>C		intron_variant	Intron 4 of 7		NP_001165883.1
VANGL1	NM_001172411.2	c.806+4874T>C		intron_variant	Intron 4 of 7		NP_001165882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VANGL1	ENST00000355485.7	c.812+4874T>C		intron_variant	Intron 4 of 7	1	NM_138959.3	ENSP00000347672.2
VANGL1	ENST00000310260.7	c.812+4874T>C		intron_variant	Intron 4 of 7	1		ENSP00000310800.3
VANGL1	ENST00000369509.1	c.812+4874T>C		intron_variant	Intron 3 of 6	1		ENSP00000358522.1
VANGL1	ENST00000369510.8	c.806+4874T>C		intron_variant	Intron 4 of 7	1		ENSP00000358523.3

Frequencies

GnomAD3 genomes AF: 0.0832 AC: 12649 AN: 152072 Hom.: 541 Cov.: 33

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0640

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.0506

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0908

Gnomad OTH AF: 0.0968

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0831 AC: 12651 AN: 152190 Hom.: 542 Cov.: 33 AF XY: 0.0845 AC XY: 6290 AN XY: 74422

African (AFR) AF: 0.0672 AC: 2790 AN: 41508

American (AMR) AF: 0.0639 AC: 977 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0775 AC: 269 AN: 3472

East Asian (EAS) AF: 0.152 AC: 788 AN: 5178

South Asian (SAS) AF: 0.0509 AC: 245 AN: 4818

European-Finnish (FIN) AF: 0.103 AC: 1095 AN: 10606

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.0908 AC: 6175 AN: 68012

Other (OTH) AF: 0.0954 AC: 201 AN: 2108

Alfa AF: 0.0857 Hom.: 858

Bravo AF: 0.0802

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.81
PhyloP100		0.21
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: rs17500488; hg19: chr1-116211763;