1-107418537-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001113226.3(NTNG1):c.1087+10829A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,374,710 control chromosomes in the GnomAD database, including 17,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1720 hom., cov: 32)
  • Exomes 𝑓: 0.15 (15323 hom.)
• Consequence: NTNG1 NM_001113226.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.401

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=-0.32).
• BP6: Variant 1-107418537-A-G is Benign according to our data. Variant chr1-107418537-A-G is described in ClinVar as [Benign]. Clinvar id is 1250495.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTNG1	NM_001113226.3	c.1087+10829A>G		intron_variant		ENST00000370068.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTNG1	ENST00000370068.6	c.1087+10829A>G		intron_variant		5	NM_001113226.3	P1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22201 AN: 151834 Hom.: 1721 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.0210

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.151

GnomAD3 exomes AF: 0.151 AC: 25689 AN: 170122 Hom.: 2119 AF XY: 0.150 AC XY: 13549 AN XY: 90328

Gnomad AFR exome AF: 0.127

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.0198

Gnomad SAS exome AF: 0.151

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.166

Gnomad OTH exome AF: 0.168

GnomAD4 exome AF: 0.154 AC: 188104 AN: 1222758 Hom.: 15323 Cov.: 16 AF XY: 0.154 AC XY: 94308 AN XY: 612188

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.192

Gnomad4 ASJ exome AF: 0.192

Gnomad4 EAS exome AF: 0.0306

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.146 AC: 22205 AN: 151952 Hom.: 1720 Cov.: 32 AF XY: 0.144 AC XY: 10659 AN XY: 74264

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.0209

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.150

Alfa AF: 0.160 Hom.: 1088

Bravo AF: 0.151

Asia WGS AF: 0.107 AC: 371 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
Cadd	Benign	13
Dann	Benign	0.67

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: rs12731224; hg19: chr1-107961159; COSMIC: COSV64270491;