rs17505688

Variant names:

• chr1-107156419-T-C
• rs17505688
• NM_001113226.3:c.246+7580T>C

Variant summary

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

The NM_001113226.3(NTNG1):​c.246+7580T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 152,166 control chromosomes in the GnomAD database, including 257 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 0.051 (257 hom., cov: 32)
• Consequence: NTNG1 NM_001113226.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121
• Publications: 5 publications found

Genes affected

NTNG1 (HGNC:23319): (netrin G1) This gene encodes a preproprotein that is processed into a secreted protein containing eukaroytic growth factor (EGF)-like domains. This protein acts to guide axon growth during neuronal development. Polymorphisms in this gene may be associated with schizophrenia. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2015]

NTNG1 Gene-Disease associations (from GenCC):

• atypical Rett syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTNG1	NM_001113226.3	c.246+7580T>C		intron_variant	Intron 2 of 7	ENST00000370068.6	NP_001106697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTNG1	ENST00000370068.6	c.246+7580T>C		intron_variant	Intron 2 of 7	5	NM_001113226.3	ENSP00000359085.1

Frequencies

GnomAD3 genomes AF: 0.0509 AC: 7744 AN: 152048 Hom.: 257 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0401

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0419

Gnomad FIN AF: 0.0794

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0772

Gnomad OTH AF: 0.0508

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

GnomAD4 genome AF: 0.0509 AC: 7744 AN: 152166 Hom.: 257 Cov.: 32 AF XY: 0.0501 AC XY: 3728 AN XY: 74382

African (AFR) AF: 0.0146 AC: 606 AN: 41530

American (AMR) AF: 0.0402 AC: 614 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0242 AC: 84 AN: 3470

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5182

South Asian (SAS) AF: 0.0419 AC: 202 AN: 4820

European-Finnish (FIN) AF: 0.0794 AC: 840 AN: 10584

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0772 AC: 5251 AN: 67990

Other (OTH) AF: 0.0498 AC: 105 AN: 2110

Alfa AF: 0.0681 Hom.: 192

Bravo AF: 0.0463

Asia WGS AF: 0.0220 AC: 78 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.34
PhyloP100		0.12
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: rs17505688; hg19: chr1-107699041;