rs17018956

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NTNG1	NM_001113226.3	c.1087+8727G>A		intron_variant		ENST00000370068.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTNG1	ENST00000370068.6	c.1087+8727G>A		intron_variant		5	NM_001113226.3	P1

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

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.0211

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.154

Alfa AF: 0.0775 Hom.: 77

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

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: rs17018956; hg19: chr1-107959057;