chr17-9028802-A-G

Variant names:

• chr17-9028802-A-G
• rs4791774
• NM_004822.3:c.1018+5411A>G

Variant summary

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

The NM_004822.3(NTN1):​c.1018+5411A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 152,054 control chromosomes in the GnomAD database, including 18,803 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 0.49 (18803 hom., cov: 33)
• Consequence: NTN1 NM_004822.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195
• Publications: 24 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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTN1	NM_004822.3	c.1018+5411A>G		intron_variant	Intron 2 of 6	ENST00000173229.7	NP_004813.2
NTN1	XM_006721595.4	c.1018+5411A>G		intron_variant	Intron 2 of 6		XP_006721658.1
NTN1	XM_047437096.1	c.1018+5411A>G		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+5411A>G		intron_variant	Intron 2 of 6	1	NM_004822.3	ENSP00000173229.2

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74457 AN: 151936 Hom.: 18784 Cov.: 33

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.490 AC: 74519 AN: 152054 Hom.: 18803 Cov.: 33 AF XY: 0.489 AC XY: 36356 AN XY: 74336

African (AFR) AF: 0.586 AC: 24300 AN: 41456

American (AMR) AF: 0.504 AC: 7707 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1524 AN: 3464

East Asian (EAS) AF: 0.188 AC: 975 AN: 5184

South Asian (SAS) AF: 0.448 AC: 2158 AN: 4820

European-Finnish (FIN) AF: 0.448 AC: 4729 AN: 10564

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31529 AN: 67970

Other (OTH) AF: 0.497 AC: 1052 AN: 2116

Alfa AF: 0.466 Hom.: 47558

Bravo AF: 0.496

Asia WGS AF: 0.357 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.1
DANN	Benign	0.52
PhyloP100		0.20
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: rs4791774; hg19: chr17-8932119;