chr1-107148301-A-G

Position:

• chr1-107148301-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001113226.3(NTNG1):​c.-293A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0549 in 285,200 control chromosomes in the GnomAD database, including 560 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.051 (252 hom., cov: 32)
  • Exomes 𝑓: 0.060 (308 hom.)
• Consequence: NTNG1 NM_001113226.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.342

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-107148301-A-G is Benign according to our data. Variant chr1-107148301-A-G is described in ClinVar as [Benign]. Clinvar id is 1225285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-107148301-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTNG1	NM_001113226.3	c.-293A>G		5_prime_UTR_variant	2/8	ENST00000370068.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTNG1	ENST00000370068.6	c.-293A>G		5_prime_UTR_variant	2/8	5	NM_001113226.3	P1

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 7723 AN: 152132 Hom.: 252 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0400

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0420

Gnomad FIN AF: 0.0792

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0770

Gnomad OTH AF: 0.0502

GnomAD4 exome AF: 0.0597 AC: 7933 AN: 132950 Hom.: 308 Cov.: 0 AF XY: 0.0593 AC XY: 4085 AN XY: 68870

Gnomad4 AFR exome AF: 0.0127

Gnomad4 AMR exome AF: 0.0435

Gnomad4 ASJ exome AF: 0.0263

Gnomad4 EAS exome AF: 0.00398

Gnomad4 SAS exome AF: 0.0416

Gnomad4 FIN exome AF: 0.0886

Gnomad4 NFE exome AF: 0.0717

Gnomad4 OTH exome AF: 0.0575

GnomAD4 genome AF: 0.0507 AC: 7723 AN: 152250 Hom.: 252 Cov.: 32 AF XY: 0.0501 AC XY: 3733 AN XY: 74470

Gnomad4 AFR AF: 0.0145

Gnomad4 AMR AF: 0.0401

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.00366

Gnomad4 SAS AF: 0.0421

Gnomad4 FIN AF: 0.0792

Gnomad4 NFE AF: 0.0770

Gnomad4 OTH AF: 0.0492

Alfa AF: 0.0669 Hom.: 368

Bravo AF: 0.0463

Asia WGS AF: 0.0230 AC: 79 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	-0.90
CADD	Benign	4.3
DANN	Benign	0.58

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: rs17505369; hg19: chr1-107690923;