NM_004822.3:c.1018+17221T>C

Variant names:

• chr17-9040612-T-C
• rs8076457
• NM_004822.3:c.1018+17221T>C

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+17221T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 152,066 control chromosomes in the GnomAD database, including 46,824 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 0.78 (46824 hom., cov: 31)
• Consequence: NTN1 NM_004822.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.651
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 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+17221T>C		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+17221T>C		intron	N/A	ENSP00000173229.2

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118903 AN: 151948 Hom.: 46772 Cov.: 31

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.765

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

GnomAD4 genome AF: 0.783 AC: 119017 AN: 152066 Hom.: 46824 Cov.: 31 AF XY: 0.789 AC XY: 58658 AN XY: 74350

African (AFR) AF: 0.824 AC: 34193 AN: 41494

American (AMR) AF: 0.815 AC: 12454 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2316 AN: 3470

East Asian (EAS) AF: 0.966 AC: 5011 AN: 5188

South Asian (SAS) AF: 0.820 AC: 3948 AN: 4816

European-Finnish (FIN) AF: 0.818 AC: 8627 AN: 10552

Middle Eastern (MID) AF: 0.784 AC: 229 AN: 292

European-Non Finnish (NFE) AF: 0.734 AC: 49866 AN: 67954

Other (OTH) AF: 0.765 AC: 1610 AN: 2104

Alfa AF: 0.759 Hom.: 41158

Bravo AF: 0.785

Asia WGS AF: 0.878 AC: 3041 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.56
PhyloP100		-0.65
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: rs8076457; hg19: chr17-8943929; COSMIC: COSV51487309;