rs17018956

Variant names:

• chr1-107416435-G-A
• rs17018956
• NM_001113226.3:c.1087+8727G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-107416435-G-A
• chr1-107416435-G-T

Variant summary

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

The NM_001113226.3(NTNG1):​c.1087+8727G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 151,972 control chromosomes in the GnomAD database, including 1,780 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 0.15 (1780 hom., cov: 32)
• Consequence: NTNG1 NM_001113226.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTNG1	NM_001113226.3	c.1087+8727G>A		intron_variant	Intron 5 of 7	ENST00000370068.6	NP_001106697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTNG1	ENST00000370068.6	c.1087+8727G>A		intron_variant	Intron 5 of 7	5	NM_001113226.3	ENSP00000359085.1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22642 AN: 151854 Hom.: 1781 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.149 AC: 22647 AN: 151972 Hom.: 1780 Cov.: 32 AF XY: 0.146 AC XY: 10860 AN XY: 74258

African (AFR) AF: 0.134 AC: 5542 AN: 41480

American (AMR) AF: 0.181 AC: 2753 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 661 AN: 3468

East Asian (EAS) AF: 0.0211 AC: 109 AN: 5178

South Asian (SAS) AF: 0.149 AC: 718 AN: 4818

European-Finnish (FIN) AF: 0.124 AC: 1306 AN: 10526

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11098 AN: 67948

Other (OTH) AF: 0.154 AC: 326 AN: 2112

Alfa AF: 0.0798 Hom.: 84

Bravo AF: 0.155

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.9
DANN	Benign	0.30
PhyloP100		0.084
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: rs17018956; hg19: chr1-107959057;