12-95713165-T-C

Position:

• chr12-95713165-T-C

Variant summary

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

The NM_021229.4(NTN4):​c.991+47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,589,396 control chromosomes in the GnomAD database, including 54,252 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 0.32 (9625 hom., cov: 31)
  • Exomes 𝑓: 0.24 (44627 hom.)
• Consequence: NTN4 NM_021229.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTN4	NM_021229.4	c.991+47A>G		intron_variant		ENST00000343702.9	NP_067052.2
NTN4	NM_001329700.2	c.991+47A>G		intron_variant			NP_001316629.1
NTN4	NM_001329701.2	c.880+47A>G		intron_variant			NP_001316630.1
NTN4	NM_001329702.2	c.880+47A>G		intron_variant			NP_001316631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTN4	ENST00000343702.9	c.991+47A>G		intron_variant		1	NM_021229.4	ENSP00000340998.4

Frequencies

GnomAD3 genomes AF: 0.323 AC: 49013 AN: 151886 Hom.: 9603 Cov.: 31

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.287

GnomAD3 exomes AF: 0.252 AC: 61843 AN: 245768 Hom.: 9684 AF XY: 0.244 AC XY: 32388 AN XY: 132874

Gnomad AFR exome AF: 0.558

Gnomad AMR exome AF: 0.149

Gnomad ASJ exome AF: 0.234

Gnomad EAS exome AF: 0.529

Gnomad SAS exome AF: 0.169

Gnomad FIN exome AF: 0.252

Gnomad NFE exome AF: 0.217

Gnomad OTH exome AF: 0.228

GnomAD4 exome AF: 0.237 AC: 340037 AN: 1437392 Hom.: 44627 Cov.: 30 AF XY: 0.233 AC XY: 165786 AN XY: 710592

Gnomad4 AFR exome AF: 0.557

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.233

Gnomad4 EAS exome AF: 0.539

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.253

Gnomad4 NFE exome AF: 0.223

Gnomad4 OTH exome AF: 0.255

GnomAD4 genome AF: 0.323 AC: 49071 AN: 152004 Hom.: 9625 Cov.: 31 AF XY: 0.319 AC XY: 23700 AN XY: 74290

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.290

Alfa AF: 0.229 Hom.: 9466

Bravo AF: 0.334

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.28
DANN	Benign	0.28

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: rs4129599; hg19: chr12-96106943;