1-107325019-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001113226.3(NTNG1):c.887+97C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 1,263,522 control chromosomes in the GnomAD database, including 714 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (81 hom., cov: 32)
  • Exomes 𝑓: 0.030 (633 hom.)
• Consequence: NTNG1 NM_001113226.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0670

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-107325019-C-T is Benign according to our data. Variant chr1-107325019-C-T is described in ClinVar as [Benign]. Clinvar id is 1274913.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0239 (3630/152200) while in subpopulation NFE AF= 0.0343 (2333/68012). AF 95% confidence interval is 0.0331. There are 81 homozygotes in gnomad4. There are 1861 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 81 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTNG1	NM_001113226.3	c.887+97C>T		intron_variant		ENST00000370068.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTNG1	ENST00000370068.6	c.887+97C>T		intron_variant		5	NM_001113226.3	P1

Frequencies

GnomAD3 genomes AF: 0.0239 AC: 3632 AN: 152082 Hom.: 81 Cov.: 32

Gnomad AFR AF: 0.00570

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0196

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0343

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.0296 AC: 32914 AN: 1111322 Hom.: 633 AF XY: 0.0287 AC XY: 15894 AN XY: 554254

Gnomad4 AFR exome AF: 0.00424

Gnomad4 AMR exome AF: 0.0135

Gnomad4 ASJ exome AF: 0.00952

Gnomad4 EAS exome AF: 0.0000265

Gnomad4 SAS exome AF: 0.00302

Gnomad4 FIN exome AF: 0.0655

Gnomad4 NFE exome AF: 0.0334

Gnomad4 OTH exome AF: 0.0234

GnomAD4 genome AF: 0.0239 AC: 3630 AN: 152200 Hom.: 81 Cov.: 32 AF XY: 0.0250 AC XY: 1861 AN XY: 74406

Gnomad4 AFR AF: 0.00566

Gnomad4 AMR AF: 0.0195

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.0637

Gnomad4 NFE AF: 0.0343

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0353 Hom.: 24

Bravo AF: 0.0191

Asia WGS AF: 0.00318 AC: 11 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 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.3
Dann	Benign	0.44

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: rs113825565; hg19: chr1-107867641;