rs9909240

Variant names:

• chr17-9236774-G-A
• rs9909240
• NM_004822.3:c.1487-2866G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004822.3(NTN1):​c.1487-2866G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,132 control chromosomes in the GnomAD database, including 20,574 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 0.50 (20574 hom., cov: 32)
• Consequence: NTN1 NM_004822.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 6 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

LOC124903923 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.634 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTN1	NM_004822.3	MANE Select	c.1487-2866G>A		intron	N/A	NP_004813.2	O95631

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTN1	ENST00000173229.7	TSL:1 MANE Select	c.1487-2866G>A		intron	N/A	ENSP00000173229.2	O95631
	NTN1	ENST00000962853.1		c.1487-2866G>A		intron	N/A	ENSP00000632912.1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75476 AN: 152016 Hom.: 20577 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.496 AC: 75494 AN: 152132 Hom.: 20574 Cov.: 32 AF XY: 0.488 AC XY: 36279 AN XY: 74372

African (AFR) AF: 0.294 AC: 12224 AN: 41518

American (AMR) AF: 0.494 AC: 7553 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1928 AN: 3468

East Asian (EAS) AF: 0.188 AC: 975 AN: 5178

South Asian (SAS) AF: 0.535 AC: 2578 AN: 4822

European-Finnish (FIN) AF: 0.477 AC: 5046 AN: 10578

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43403 AN: 67964

Other (OTH) AF: 0.516 AC: 1088 AN: 2110

Alfa AF: 0.607 Hom.: 16691

Bravo AF: 0.486

Asia WGS AF: 0.381 AC: 1326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.14
DANN	Benign	0.61
PhyloP100		-1.6
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: rs9909240; hg19: chr17-9140091; COSMIC: COSV51487990;