rs3785982

Variant names:

• chr17-9186907-C-T
• rs3785982
• NM_004822.3:c.1411+3938C>T

Variant summary

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

The NM_004822.3(NTN1):​c.1411+3938C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0839 in 152,024 control chromosomes in the GnomAD database, including 743 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 0.084 (743 hom., cov: 32)
• Consequence: NTN1 NM_004822.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTN1	NM_004822.3	c.1411+3938C>T		intron_variant	Intron 5 of 6	ENST00000173229.7	NP_004813.2
NTN1	XM_006721595.4	c.1411+3938C>T		intron_variant	Intron 5 of 6		XP_006721658.1
NTN1	XM_047437096.1	c.1411+3938C>T		intron_variant	Intron 5 of 6		XP_047293052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTN1	ENST00000173229.7	c.1411+3938C>T		intron_variant	Intron 5 of 6	1	NM_004822.3	ENSP00000173229.2

Frequencies

GnomAD3 genomes AF: 0.0840 AC: 12754 AN: 151906 Hom.: 743 Cov.: 32

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.0771

Gnomad AMR AF: 0.0837

Gnomad ASJ AF: 0.0752

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0748

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

GnomAD4 genome AF: 0.0839 AC: 12762 AN: 152024 Hom.: 743 Cov.: 32 AF XY: 0.0859 AC XY: 6383 AN XY: 74292

African (AFR) AF: 0.0205 AC: 849 AN: 41456

American (AMR) AF: 0.0835 AC: 1275 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0752 AC: 261 AN: 3472

East Asian (EAS) AF: 0.199 AC: 1026 AN: 5146

South Asian (SAS) AF: 0.153 AC: 737 AN: 4818

European-Finnish (FIN) AF: 0.122 AC: 1289 AN: 10564

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.104 AC: 7077 AN: 67990

Other (OTH) AF: 0.0754 AC: 159 AN: 2108

Alfa AF: 0.0949 Hom.: 1064

Bravo AF: 0.0791

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
DANN	Benign	0.46
PhyloP100		0.0060
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: rs3785982; hg19: chr17-9090224;