17-9173220-C-G

Variant names:

• chr17-9173220-C-G
• rs11870124
• ENST00000574307.2:n.4797G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000574307.2(ENSG00000262966):​n.4797G>C variant causes a non coding transcript exon 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: ENSG00000262966 ENST00000574307.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• Publications: 2 publications found

Genes affected

ENSG00000262966 (HGNC:):

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=-0.89).
• 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 rank	MANE	Protein	UniProt
NTN1	NM_004822.3	c.1208-6587C>G		intron_variant	Intron 3 of 6	ENST00000173229.7	NP_004813.2
LOC101928266	NR_110828.1	n.4797G>C		non_coding_transcript_exon_variant	Exon 2 of 4
NTN1	XM_006721595.4	c.1208-6587C>G		intron_variant	Intron 3 of 6		XP_006721658.1
NTN1	XM_047437096.1	c.1208-6587C>G		intron_variant	Intron 3 of 6		XP_047293052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000262966	ENST00000574307.2	n.4797G>C		non_coding_transcript_exon_variant	Exon 2 of 4	1
NTN1	ENST00000173229.7	c.1208-6587C>G		intron_variant	Intron 3 of 6	1	NM_004822.3	ENSP00000173229.2
NTN1	ENST00000436734.1	c.68-6587C>G		intron_variant	Intron 1 of 3	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

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.625 AC: 5 AN: 8

South Asian (SAS) AF: 0.250 AC: 1 AN: 4

European-Finnish (FIN) AF: 0.0500 AC: 5 AN: 100

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 6

European-Non Finnish (NFE) AF: 0.129 AC: 22 AN: 170

Other (OTH) AF: 0.0833 AC: 2 AN: 24

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

African (AFR) AF: 0.188 AC: 7791 AN: 41484

American (AMR) AF: 0.201 AC: 3066 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 416 AN: 3468

East Asian (EAS) AF: 0.386 AC: 1991 AN: 5154

South Asian (SAS) AF: 0.163 AC: 785 AN: 4822

European-Finnish (FIN) AF: 0.0991 AC: 1050 AN: 10600

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10185 AN: 67994

Other (OTH) AF: 0.161 AC: 339 AN: 2112

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
PhyloP100		-0.15
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: rs11870124; hg19: chr17-9076537;