rs4791331

Positions:

• chr17-9028765-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
NTN1	NM_004822.3	c.1018+5374C>T		intron_variant		ENST00000173229.7	NP_004813.2
NTN1	XM_006721595.4	c.1018+5374C>T		intron_variant			XP_006721658.1
NTN1	XM_047437096.1	c.1018+5374C>T		intron_variant			XP_047293052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTN1	ENST00000173229.7	c.1018+5374C>T		intron_variant		1	NM_004822.3	ENSP00000173229	P1

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

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.464

Gnomad4 OTH AF: 0.508

Alfa AF: 0.481 Hom.: 9064

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

Uncertain significance, no assertion criteria provided

in vitro;in vivo

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University

Jan 02, 2019

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2021

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4791331; hg19: chr17-8932082;