rs4791331

Variant names:

• chr17-9028765-C-T
• rs4791331
• NM_004822.3:c.1018+5374C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_004822.3(NTN1):​c.1018+5374C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,042 control chromosomes in the GnomAD database, including 21,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (21610 hom., cov: 32)
• Consequence: NTN1 NM_004822.3 intron
• Clinical Significance: Benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 1.81
• Publications: 10 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=-0.38).
• BP6: Variant 17-9028765-C-T is Benign according to our data. Variant chr17-9028765-C-T is described in ClinVar as Benign. ClinVar VariationId is 692209.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTN1	NM_004822.3	c.1018+5374C>T		intron_variant	Intron 2 of 6	ENST00000173229.7	NP_004813.2
NTN1	XM_006721595.4	c.1018+5374C>T		intron_variant	Intron 2 of 6		XP_006721658.1
NTN1	XM_047437096.1	c.1018+5374C>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+5374C>T		intron_variant	Intron 2 of 6	1	NM_004822.3	ENSP00000173229.2

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78847 AN: 151924 Hom.: 21588 Cov.: 32

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.519 AC: 78919 AN: 152042 Hom.: 21610 Cov.: 32 AF XY: 0.517 AC XY: 38408 AN XY: 74306

African (AFR) AF: 0.688 AC: 28543 AN: 41478

American (AMR) AF: 0.514 AC: 7863 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1524 AN: 3472

East Asian (EAS) AF: 0.188 AC: 975 AN: 5176

South Asian (SAS) AF: 0.447 AC: 2155 AN: 4816

European-Finnish (FIN) AF: 0.448 AC: 4721 AN: 10548

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.464 AC: 31519 AN: 67946

Other (OTH) AF: 0.508 AC: 1075 AN: 2116

Alfa AF: 0.482 Hom.: 10112

Bravo AF: 0.529

Asia WGS AF: 0.360 AC: 1257 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Nonsyndromic cleft lip with or without cleft palate Uncertain:1

Jan 02, 2019

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: in vitro;in vivo

- -

not provided Benign:1

Feb 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 31780810) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.69
PhyloP100		1.8
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: rs4791331; hg19: chr17-8932082;