chr1-115651261-T-TC

Position:

• chr1-115651261-T-TC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_138959.3(VANGL1):​c.-137-11dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 661,980 control chromosomes in the GnomAD database, including 636 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.044 (465 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (171 hom.)
• Consequence: VANGL1 NM_138959.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.40

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 -10 ACMG points.

• BP6: Variant 1-115651261-T-TC is Benign according to our data. Variant chr1-115651261-T-TC is described in ClinVar as [Benign]. Clinvar id is 1301804.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VANGL1	NM_138959.3	c.-137-11dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000355485.7
VANGL1	NM_001172411.2	c.-137-11dup		splice_polypyrimidine_tract_variant, intron_variant
VANGL1	NM_001172412.2	c.-137-11dup		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VANGL1	ENST00000355485.7	c.-137-11dup		splice_polypyrimidine_tract_variant, intron_variant		1	NM_138959.3	P3
VANGL1	ENST00000310260.7	c.-137-11dup		splice_polypyrimidine_tract_variant, intron_variant		1		P3
VANGL1	ENST00000369510.8	c.-137-11dup		splice_polypyrimidine_tract_variant, intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.0434 AC: 6566 AN: 151228 Hom.: 460 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0193

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.00643

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0274

GnomAD4 exome AF: 0.00644 AC: 3288 AN: 510634 Hom.: 171 Cov.: 6 AF XY: 0.00584 AC XY: 1605 AN XY: 274918

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.0109

Gnomad4 ASJ exome AF: 0.00336

Gnomad4 EAS exome AF: 0.00121

Gnomad4 SAS exome AF: 0.00572

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000600

Gnomad4 OTH exome AF: 0.0143

GnomAD4 genome AF: 0.0436 AC: 6594 AN: 151346 Hom.: 465 Cov.: 32 AF XY: 0.0420 AC XY: 3105 AN XY: 73976

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.0193

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00270

Gnomad4 SAS AF: 0.00643

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000633

Gnomad4 OTH AF: 0.0271

Alfa AF: 0.0276 Hom.: 18

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Dec 30, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs199829701; hg19: chr1-116193882;