17-9026528-A-G

Variant names:

• chr17-9026528-A-G
• rs1880646
• NM_004822.3:c.1018+3137A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004822.3(NTN1):​c.1018+3137A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 151,900 control chromosomes in the GnomAD database, including 7,112 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (7112 hom., cov: 31)
• Consequence: NTN1 NM_004822.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• Publications: 11 publications found

Genes affected

NTN1 (HGNC:8029): (netrin 1) Netrin is included in a family of laminin-related secreted proteins. The function of this gene has not yet been defined; however, netrin is thought to be involved in axon guidance and cell migration during development. Mutations and loss of expression of netrin suggest that variation in netrin may be involved in cancer development. [provided by RefSeq, Jul 2008]

NTN1 Gene-Disease associations (from GenCC):

• mirror movements 4

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial congenital mirror movements

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004822.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTN1	NM_004822.3	MANE Select	c.1018+3137A>G		intron	N/A	NP_004813.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTN1	ENST00000173229.7	TSL:1 MANE Select	c.1018+3137A>G		intron	N/A	ENSP00000173229.2
	NTN1	ENST00000962853.1		c.1018+3137A>G		intron	N/A	ENSP00000632912.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45762 AN: 151782 Hom.: 7110 Cov.: 31

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.317

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.301 AC: 45771 AN: 151900 Hom.: 7112 Cov.: 31 AF XY: 0.301 AC XY: 22338 AN XY: 74226

African (AFR) AF: 0.321 AC: 13282 AN: 41400

American (AMR) AF: 0.295 AC: 4496 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1213 AN: 3466

East Asian (EAS) AF: 0.537 AC: 2774 AN: 5166

South Asian (SAS) AF: 0.294 AC: 1415 AN: 4816

European-Finnish (FIN) AF: 0.293 AC: 3078 AN: 10522

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18467 AN: 67972

Other (OTH) AF: 0.324 AC: 682 AN: 2104

Alfa AF: 0.273 Hom.: 3430

Bravo AF: 0.304

Asia WGS AF: 0.419 AC: 1456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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: rs1880646; hg19: chr17-8929845;