chr17-9040612-T-C

Position:

• chr17-9040612-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTN1	NM_004822.3	c.1018+17221T>C		intron_variant		ENST00000173229.7	NP_004813.2
NTN1	XM_006721595.4	c.1018+17221T>C		intron_variant			XP_006721658.1
NTN1	XM_047437096.1	c.1018+17221T>C		intron_variant			XP_047293052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTN1	ENST00000173229.7	c.1018+17221T>C		intron_variant		1	NM_004822.3	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

Gnomad4 AFR AF: 0.824

Gnomad4 AMR AF: 0.815

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.966

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.765

Alfa AF: 0.733 Hom.: 19428

Bravo AF: 0.785

Asia WGS AF: 0.878 AC: 3041 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.56

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: rs8076457; hg19: chr17-8943929; COSMIC: COSV51487309;