12-95768510-C-T

Variant names:

• chr12-95768510-C-T
• rs4237913
• NM_021229.4:c.585+18429G>A

Variant summary

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

The NM_021229.4(NTN4):​c.585+18429G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.851 in 151,800 control chromosomes in the GnomAD database, including 55,042 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 0.85 (55042 hom., cov: 28)
• Consequence: NTN4 NM_021229.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597
• Publications: 0 publications found

Genes affected

NTN4 (HGNC:13658): (netrin 4) This gene encodes a member of the netrin family of proteins, which function in various biological processes including axon guidance, tumorogenesis, and angiogenesis. Netrins are laminin-related proteins that have an N-terminal laminin-type domain, epidermal growth factor-like repeat domain, and a positively charged heparin-binding domain at the C-terminus. The protein encoded by this gene is involved in processes including neurite growth and migration, angiogenesis and mural cell adhesion to endothelial cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

LINC02410 (HGNC:53339): (long intergenic non-protein coding RNA 2410)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021229.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTN4	NM_021229.4	MANE Select	c.585+18429G>A		intron	N/A	NP_067052.2
	NTN4	NM_001329700.2		c.585+18429G>A		intron	N/A	NP_001316629.1
	NTN4	NM_001329701.2		c.474+18429G>A		intron	N/A	NP_001316630.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTN4	ENST00000343702.9	TSL:1 MANE Select	c.585+18429G>A		intron	N/A	ENSP00000340998.4
	NTN4	ENST00000553059.1	TSL:1	c.585+18429G>A		intron	N/A	ENSP00000447292.1
	NTN4	ENST00000674345.1		c.585+18429G>A		intron	N/A	ENSP00000501488.1

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129148 AN: 151682 Hom.: 54992 Cov.: 28

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.827

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.847

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

GnomAD4 genome AF: 0.851 AC: 129252 AN: 151800 Hom.: 55042 Cov.: 28 AF XY: 0.851 AC XY: 63148 AN XY: 74174

African (AFR) AF: 0.881 AC: 36425 AN: 41368

American (AMR) AF: 0.827 AC: 12609 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2925 AN: 3470

East Asian (EAS) AF: 0.800 AC: 4093 AN: 5118

South Asian (SAS) AF: 0.918 AC: 4409 AN: 4802

European-Finnish (FIN) AF: 0.812 AC: 8548 AN: 10532

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.844 AC: 57374 AN: 67958

Other (OTH) AF: 0.846 AC: 1781 AN: 2106

Alfa AF: 0.845 Hom.: 89734

Bravo AF: 0.849

Asia WGS AF: 0.868 AC: 3020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.0
DANN	Benign	0.22
PhyloP100		0.60
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: rs4237913; hg19: chr12-96162288;