rs628117

Variant names:

• chr1-107454484-C-T
• rs628117
• NM_001113226.3:c.1390+17685C>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.1390+17685C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,772 control chromosomes in the GnomAD database, including 24,075 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 0.56 (24075 hom., cov: 31)
• Consequence: NTNG1 NM_001113226.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.61
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTNG1	NM_001113226.3	c.1390+17685C>T		intron_variant	Intron 7 of 7	ENST00000370068.6	NP_001106697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTNG1	ENST00000370068.6	c.1390+17685C>T		intron_variant	Intron 7 of 7	5	NM_001113226.3	ENSP00000359085.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84994 AN: 151654 Hom.: 24065 Cov.: 31

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.560 AC: 85054 AN: 151772 Hom.: 24075 Cov.: 31 AF XY: 0.560 AC XY: 41522 AN XY: 74124

African (AFR) AF: 0.530 AC: 21946 AN: 41392

American (AMR) AF: 0.613 AC: 9354 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2123 AN: 3470

East Asian (EAS) AF: 0.687 AC: 3522 AN: 5124

South Asian (SAS) AF: 0.668 AC: 3214 AN: 4810

European-Finnish (FIN) AF: 0.461 AC: 4844 AN: 10502

Middle Eastern (MID) AF: 0.613 AC: 179 AN: 292

European-Non Finnish (NFE) AF: 0.561 AC: 38093 AN: 67900

Other (OTH) AF: 0.584 AC: 1233 AN: 2110

Alfa AF: 0.570 Hom.: 42238

Bravo AF: 0.570

Asia WGS AF: 0.647 AC: 2248 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0020
DANN	Benign	0.57
PhyloP100		-4.6
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: rs628117; hg19: chr1-107997106;