chr1-107325019-C-T

Variant names:

• chr1-107325019-C-T
• rs113825565
• NM_001113226.3:c.887+97C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0670
• Publications: 1 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 -20 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 VariationId is 1274913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3630 AD gene.

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.887+97C>T		intron	N/A	NP_001106697.1	Q9Y2I2-3
	NTNG1	NM_001372167.1		c.887+97C>T		intron	N/A	NP_001359096.1	Q9Y2I2-3
	NTNG1	NM_001372170.1		c.887+97C>T		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.887+97C>T		intron	N/A	ENSP00000359085.1	Q9Y2I2-3
	NTNG1	ENST00000370066.5	TSL:1	c.887+97C>T		intron	N/A	ENSP00000359083.1	Q9Y2I2-4
	NTNG1	ENST00000370074.8	TSL:1	c.887+97C>T		intron	N/A	ENSP00000359091.3	Q9Y2I2-1

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

African (AFR) AF: 0.00424 AC: 107 AN: 25234

American (AMR) AF: 0.0135 AC: 392 AN: 28978

Ashkenazi Jewish (ASJ) AF: 0.00952 AC: 175 AN: 18390

East Asian (EAS) AF: 0.0000265 AC: 1 AN: 37670

South Asian (SAS) AF: 0.00302 AC: 192 AN: 63484

European-Finnish (FIN) AF: 0.0655 AC: 2693 AN: 41090

Middle Eastern (MID) AF: 0.00493 AC: 16 AN: 3244

European-Non Finnish (NFE) AF: 0.0334 AC: 28218 AN: 845288

Other (OTH) AF: 0.0234 AC: 1120 AN: 47944

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

African (AFR) AF: 0.00566 AC: 235 AN: 41552

American (AMR) AF: 0.0195 AC: 298 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00187 AC: 9 AN: 4822

European-Finnish (FIN) AF: 0.0637 AC: 676 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0343 AC: 2333 AN: 68012

Other (OTH) AF: 0.0194 AC: 41 AN: 2112

Alfa AF: 0.0353 Hom.: 24

Bravo AF: 0.0191

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.44
PhyloP100		0.067
Mutation Taster		=100/0	polymorphism

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: rs113825565; hg19: chr1-107867641;