1-107418574-G-A

Variant summary

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

The ENST00000370066.5(NTNG1):c.1088-6G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 1,589,884 control chromosomes in the GnomAD database, including 3,569 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.048 (247 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3322 hom.)
• Consequence: NTNG1 ENST00000370066.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001023
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.39

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=-0.36).
• BP6: Variant 1-107418574-G-A is Benign according to our data. Variant chr1-107418574-G-A is described in ClinVar as [Benign]. Clinvar id is 1241235.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-107418574-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTNG1	NM_001113226.3	c.1087+10866G>A		intron_variant		ENST00000370068.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTNG1	ENST00000370068.6	c.1087+10866G>A		intron_variant		5	NM_001113226.3	P1

Frequencies

GnomAD3 genomes AF: 0.0478 AC: 7263 AN: 151818 Hom.: 248 Cov.: 32

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0425

Gnomad ASJ AF: 0.0933

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.0255

Gnomad FIN AF: 0.0611

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0710

Gnomad OTH AF: 0.0484

GnomAD3 exomes AF: 0.0512 AC: 11639 AN: 227496 Hom.: 362 AF XY: 0.0516 AC XY: 6334 AN XY: 122716

Gnomad AFR exome AF: 0.0110

Gnomad AMR exome AF: 0.0354

Gnomad ASJ exome AF: 0.0954

Gnomad EAS exome AF: 0.000240

Gnomad SAS exome AF: 0.0262

Gnomad FIN exome AF: 0.0591

Gnomad NFE exome AF: 0.0700

Gnomad OTH exome AF: 0.0657

GnomAD4 exome AF: 0.0640 AC: 92076 AN: 1437948 Hom.: 3322 Cov.: 28 AF XY: 0.0634 AC XY: 45253 AN XY: 714020

Gnomad4 AFR exome AF: 0.0112

Gnomad4 AMR exome AF: 0.0365

Gnomad4 ASJ exome AF: 0.0940

Gnomad4 EAS exome AF: 0.000102

Gnomad4 SAS exome AF: 0.0259

Gnomad4 FIN exome AF: 0.0561

Gnomad4 NFE exome AF: 0.0717

Gnomad4 OTH exome AF: 0.0616

GnomAD4 genome AF: 0.0478 AC: 7257 AN: 151936 Hom.: 247 Cov.: 32 AF XY: 0.0460 AC XY: 3416 AN XY: 74248

Gnomad4 AFR AF: 0.0134

Gnomad4 AMR AF: 0.0424

Gnomad4 ASJ AF: 0.0933

Gnomad4 EAS AF: 0.000969

Gnomad4 SAS AF: 0.0255

Gnomad4 FIN AF: 0.0611

Gnomad4 NFE AF: 0.0709

Gnomad4 OTH AF: 0.0479

Alfa AF: 0.0678 Hom.: 502

Bravo AF: 0.0464

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 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	15
Dann	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.010
SpliceAI score (max)		0.020		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: rs17530804; hg19: chr1-107961196;