Variant rs4129599 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_021229.4(NTN4):c.991+47A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000743 in 1,590,724 control chromosomes in the GnomAD database, including 24 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 0.0016 ( 4 hom., cov: 31)

Exomes 𝑓: 0.00065 ( 20 hom. )

Consequence

NTN4
NM_021229.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.232

Variant links:

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]

NTN4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00158 (240/152064) while in subpopulation EAS AF= 0.0342 (177/5170). AF 95% confidence interval is 0.0301. There are 4 homozygotes in gnomad4. There are 127 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
NTN4	NM_021229.4 linkuse as main transcript	c.991+47A>T	intron_variant	ENST00000343702.9	NP_067052.2	Q9HB63-1
NTN4	NM_001329700.2 linkuse as main transcript	c.991+47A>T	intron_variant		NP_001316629.1	Q9HB63-2B2RE43A8K3H6
NTN4	NM_001329701.2 linkuse as main transcript	c.880+47A>T	intron_variant		NP_001316630.1	Q9HB63-3A8K3H6
NTN4	NM_001329702.2 linkuse as main transcript	c.880+47A>T	intron_variant		NP_001316631.1	Q9HB63-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTN4	ENST00000343702.9 linkuse as main transcript	c.991+47A>T		intron_variant		1	NM_021229.4	ENSP00000340998.4		Q9HB63-1

Frequencies

GnomAD3 genomes

AF:

0.00161

AC:

244

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000983

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0349

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00272

AC:

669

AN:

245768

Hom.:

AF XY:

0.00246

AC XY:

327

AN XY:

132874

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.0000889

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0354

Gnomad SAS exome

AF:

0.0000677

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000901

Gnomad OTH exome

AF:

0.00150

GnomAD4 exome

AF:

0.000655

AC:

942

AN:

1438660

Hom.:

Cov.:

AF XY:

0.000613

AC XY:

436

AN XY:

711190

show subpopulations

Gnomad4 AFR exome

AF:

0.000332

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0175

Gnomad4 SAS exome

AF:

0.0000709

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000914

Gnomad4 OTH exome

AF:

0.00379

GnomAD4 genome

AF:

0.00158

AC:

240

AN:

152064

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

127

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.000965

Gnomad4 AMR

AF:

0.000982

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0342

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.0000126

Hom.:

9466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.23

DANN

Benign

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over