rs10507057

Positions:

• chr12-95704679-G-A

Variant summary

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

The NM_021229.4(NTN4):​c.1180+5762C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0583 in 152,240 control chromosomes in the GnomAD database, including 681 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 0.058 (681 hom., cov: 32)
• Consequence: NTN4 NM_021229.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTN4	NM_021229.4	c.1180+5762C>T		intron_variant		ENST00000343702.9	NP_067052.2
NTN4	NM_001329700.2	c.1180+5762C>T		intron_variant			NP_001316629.1
NTN4	NM_001329701.2	c.1069+5762C>T		intron_variant			NP_001316630.1
NTN4	NM_001329702.2	c.1069+5762C>T		intron_variant			NP_001316631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTN4	ENST00000343702.9	c.1180+5762C>T		intron_variant		1	NM_021229.4	ENSP00000340998.4

Frequencies

GnomAD3 genomes AF: 0.0582 AC: 8854 AN: 152122 Hom.: 679 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.0293

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00925

Gnomad OTH AF: 0.0373

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

GnomAD4 genome AF: 0.0583 AC: 8872 AN: 152240 Hom.: 681 Cov.: 32 AF XY: 0.0573 AC XY: 4262 AN XY: 74440

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.0274

Gnomad4 ASJ AF: 0.00691

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00622

Gnomad4 FIN AF: 0.0293

Gnomad4 NFE AF: 0.00925

Gnomad4 OTH AF: 0.0364

Alfa AF: 0.0320 Hom.: 95

Bravo AF: 0.0645

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.5
DANN	Benign	0.66

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: rs10507057; hg19: chr12-96098455;