17-9162618-T-C

Variant names:

• chr17-9162618-T-C
• rs7214739
• NM_004822.3:c.1019-195T>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.1019-195T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,152 control chromosomes in the GnomAD database, including 38,339 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 0.71 (38339 hom., cov: 33)
• Consequence: NTN1 NM_004822.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173
• Publications: 8 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 = 0.812 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.1019-195T>C		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.1019-195T>C		intron	N/A	ENSP00000173229.2	O95631
	NTN1	ENST00000962853.1		c.1019-195T>C		intron	N/A	ENSP00000632912.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107735 AN: 152034 Hom.: 38309 Cov.: 33

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.709 AC: 107817 AN: 152152 Hom.: 38339 Cov.: 33 AF XY: 0.711 AC XY: 52861 AN XY: 74370

African (AFR) AF: 0.679 AC: 28178 AN: 41488

American (AMR) AF: 0.730 AC: 11167 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2478 AN: 3472

East Asian (EAS) AF: 0.833 AC: 4307 AN: 5170

South Asian (SAS) AF: 0.609 AC: 2931 AN: 4814

European-Finnish (FIN) AF: 0.788 AC: 8346 AN: 10594

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48156 AN: 67998

Other (OTH) AF: 0.701 AC: 1480 AN: 2112

Alfa AF: 0.705 Hom.: 9127

Bravo AF: 0.710

Asia WGS AF: 0.732 AC: 2547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.1
DANN	Benign	0.60
PhyloP100		-0.17
PromoterAI		-0.00060	Neutral
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: rs7214739; hg19: chr17-9065935;