chr17-9026763-C-T

Variant names:

• chr17-9026763-C-T
• rs940850
• NM_004822.3:c.1018+3372C>T

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+3372C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 151,678 control chromosomes in the GnomAD database, including 1,187 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 0.11 (1187 hom., cov: 31)
• Consequence: NTN1 NM_004822.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58
• Publications: 1 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=-0.4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTN1	NM_004822.3	c.1018+3372C>T		intron_variant	Intron 2 of 6	ENST00000173229.7	NP_004813.2
NTN1	XM_006721595.4	c.1018+3372C>T		intron_variant	Intron 2 of 6		XP_006721658.1
NTN1	XM_047437096.1	c.1018+3372C>T		intron_variant	Intron 2 of 6		XP_047293052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTN1	ENST00000173229.7	c.1018+3372C>T		intron_variant	Intron 2 of 6	1	NM_004822.3	ENSP00000173229.2

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17243 AN: 151560 Hom.: 1174 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.0613

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0990

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.114 AC: 17292 AN: 151678 Hom.: 1187 Cov.: 31 AF XY: 0.115 AC XY: 8541 AN XY: 74070

African (AFR) AF: 0.122 AC: 5051 AN: 41326

American (AMR) AF: 0.129 AC: 1951 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.0660 AC: 229 AN: 3470

East Asian (EAS) AF: 0.256 AC: 1323 AN: 5172

South Asian (SAS) AF: 0.211 AC: 1012 AN: 4798

European-Finnish (FIN) AF: 0.0613 AC: 642 AN: 10480

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0990 AC: 6726 AN: 67958

Other (OTH) AF: 0.106 AC: 223 AN: 2106

Alfa AF: 0.101 Hom.: 1077

Bravo AF: 0.118

Asia WGS AF: 0.201 AC: 696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Benign	0.84
PhyloP100		2.6
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: rs940850; hg19: chr17-8930080;