12-95713165-T-C

Variant names:

• chr12-95713165-T-C
• rs4129599
• NM_021229.4:c.991+47A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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]

PGAM1P5 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NTN4	NM_021229.4	c.991+47A>G		intron_variant	Intron 4 of 9	ENST00000343702.9	NP_067052.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTN4	ENST00000343702.9	c.991+47A>G		intron_variant	Intron 4 of 9	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

GnomAD2 exomes AF: 0.252 AC: 61843 AN: 245768 AF XY: 0.244

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 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

African (AFR) AF: 0.557 AC: 18430 AN: 33088

American (AMR) AF: 0.156 AC: 6882 AN: 44090

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 5983 AN: 25684

East Asian (EAS) AF: 0.539 AC: 20985 AN: 38944

South Asian (SAS) AF: 0.170 AC: 14407 AN: 84516

European-Finnish (FIN) AF: 0.253 AC: 13349 AN: 52790

Middle Eastern (MID) AF: 0.222 AC: 1260 AN: 5682

European-Non Finnish (NFE) AF: 0.223 AC: 243607 AN: 1093306

Other (OTH) AF: 0.255 AC: 15134 AN: 59292

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

African (AFR) AF: 0.544 AC: 22523 AN: 41432

American (AMR) AF: 0.222 AC: 3388 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3466

East Asian (EAS) AF: 0.532 AC: 2749 AN: 5170

South Asian (SAS) AF: 0.180 AC: 868 AN: 4818

European-Finnish (FIN) AF: 0.254 AC: 2681 AN: 10554

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14968 AN: 67980

Other (OTH) AF: 0.290 AC: 613 AN: 2114

Alfa AF: 0.249 Hom.: 17648

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
PhyloP100		-0.23
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: rs4129599; hg19: chr12-96106943;