17-9173220-C-G

Position:

• chr17-9173220-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004822.3(NTN1):​c.1208-6587C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,442 control chromosomes in the GnomAD database, including 2,390 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 0.17 (2388 hom., cov: 32)
  • Exomes 𝑓: 0.11 (2 hom.)
• Consequence: NTN1 NM_004822.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153

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]

ENSG00000262966 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTN1	NM_004822.3	c.1208-6587C>G		intron_variant		ENST00000173229.7	NP_004813.2
NTN1	XM_006721595.4	c.1208-6587C>G		intron_variant			XP_006721658.1
NTN1	XM_047437096.1	c.1208-6587C>G		intron_variant			XP_047293052.1
LOC101928266	NR_110828.1	n.4797G>C		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTN1	ENST00000173229.7	c.1208-6587C>G		intron_variant		1	NM_004822.3	ENSP00000173229.2
ENSG00000262966	ENST00000574307.2	n.4797G>C		non_coding_transcript_exon_variant	2/4	1
NTN1	ENST00000436734.1	c.68-6587C>G		intron_variant		5		ENSP00000389375.2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25802 AN: 152002 Hom.: 2376 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.111 AC: 36 AN: 324 Hom.: 2 Cov.: 0 AF XY: 0.131 AC XY: 28 AN XY: 214

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.625

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.0500

Gnomad4 NFE exome AF: 0.129

Gnomad4 OTH exome AF: 0.0833

GnomAD4 genome AF: 0.170 AC: 25842 AN: 152118 Hom.: 2388 Cov.: 32 AF XY: 0.170 AC XY: 12668 AN XY: 74354

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.0991

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.161

Alfa AF: 0.152 Hom.: 240

Bravo AF: 0.179

Asia WGS AF: 0.281 AC: 977 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.61

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: rs11870124; hg19: chr17-9076537;