12-95768510-C-T

Position:

• chr12-95768510-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTN4	NM_021229.4	c.585+18429G>A		intron_variant		ENST00000343702.9	NP_067052.2
NTN4	NM_001329700.2	c.585+18429G>A		intron_variant			NP_001316629.1
NTN4	NM_001329701.2	c.474+18429G>A		intron_variant			NP_001316630.1
NTN4	NM_001329702.2	c.474+18429G>A		intron_variant			NP_001316631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTN4	ENST00000343702.9	c.585+18429G>A		intron_variant		1	NM_021229.4	ENSP00000340998.4

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

Gnomad4 AFR AF: 0.881

Gnomad4 AMR AF: 0.827

Gnomad4 ASJ AF: 0.843

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.918

Gnomad4 FIN AF: 0.812

Gnomad4 NFE AF: 0.844

Gnomad4 OTH AF: 0.846

Alfa AF: 0.844 Hom.: 70924

Bravo AF: 0.849

Asia WGS AF: 0.868 AC: 3020 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.0
DANN	Benign	0.22

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: rs4237913; hg19: chr12-96162288;