1-107376803-T-C

Variant names:

• chr1-107376803-T-C
• rs6677537
• NM_001113226.3:c.888-18351T>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.888-18351T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 152,006 control chromosomes in the GnomAD database, including 26,774 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 0.59 (26774 hom., cov: 32)
• Consequence: NTNG1 NM_001113226.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113226.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTNG1	NM_001113226.3	MANE Select	c.888-18351T>C		intron	N/A	NP_001106697.1	Q9Y2I2-3
	NTNG1	NM_001372167.1		c.888-18351T>C		intron	N/A	NP_001359096.1	Q9Y2I2-3
	NTNG1	NM_001372170.1		c.888-18351T>C		intron	N/A	NP_001359099.1	Q9Y2I2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTNG1	ENST00000370068.6	TSL:5 MANE Select	c.888-18351T>C		intron	N/A	ENSP00000359085.1	Q9Y2I2-3
	NTNG1	ENST00000370066.5	TSL:1	c.888-18351T>C		intron	N/A	ENSP00000359083.1	Q9Y2I2-4
	NTNG1	ENST00000370074.8	TSL:1	c.888-18351T>C		intron	N/A	ENSP00000359091.3	Q9Y2I2-1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88944 AN: 151888 Hom.: 26773 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.585 AC: 88961 AN: 152006 Hom.: 26774 Cov.: 32 AF XY: 0.586 AC XY: 43576 AN XY: 74316

African (AFR) AF: 0.437 AC: 18120 AN: 41430

American (AMR) AF: 0.537 AC: 8208 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2222 AN: 3472

East Asian (EAS) AF: 0.604 AC: 3117 AN: 5164

South Asian (SAS) AF: 0.747 AC: 3603 AN: 4826

European-Finnish (FIN) AF: 0.644 AC: 6798 AN: 10556

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44822 AN: 67968

Other (OTH) AF: 0.591 AC: 1248 AN: 2110

Alfa AF: 0.621 Hom.: 24998

Bravo AF: 0.567

Asia WGS AF: 0.672 AC: 2332 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.1
DANN	Benign	0.42
PhyloP100		-0.089
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: rs6677537; hg19: chr1-107919425;