12-95663408-A-G

Variant names:

• chr12-95663408-A-G
• rs2367563
• NM_021229.4:c.1750+2402T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021229.4(NTN4):​c.1750+2402T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,126 control chromosomes in the GnomAD database, including 11,800 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 0.39 (11800 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: NTN4 NM_021229.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102
• Publications: 10 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:):

PGAM1P5 (HGNC:42452): (phosphoglycerate mutase 1 pseudogene 5)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021229.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTN4	NM_021229.4	MANE Select	c.1750+2402T>C		intron	N/A	NP_067052.2
	NTN4	NM_001329700.2		c.1681+2402T>C		intron	N/A	NP_001316629.1
	NTN4	NM_001329701.2		c.1639+2402T>C		intron	N/A	NP_001316630.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTN4	ENST00000343702.9	TSL:1 MANE Select	c.1750+2402T>C		intron	N/A	ENSP00000340998.4
	NTN4	ENST00000553059.1	TSL:1	c.1681+2402T>C		intron	N/A	ENSP00000447292.1
	PGAM1P5	ENST00000552554.2	TSL:1	n.212-2275A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59777 AN: 152008 Hom.: 11794 Cov.: 33

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.389

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.393 AC: 59799 AN: 152126 Hom.: 11800 Cov.: 33 AF XY: 0.396 AC XY: 29463 AN XY: 74360

African (AFR) AF: 0.410 AC: 17033 AN: 41504

American (AMR) AF: 0.389 AC: 5951 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1338 AN: 3470

East Asian (EAS) AF: 0.521 AC: 2699 AN: 5182

South Asian (SAS) AF: 0.450 AC: 2166 AN: 4814

European-Finnish (FIN) AF: 0.380 AC: 4023 AN: 10578

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25268 AN: 67972

Other (OTH) AF: 0.388 AC: 821 AN: 2114

Alfa AF: 0.379 Hom.: 35907

Bravo AF: 0.391

Asia WGS AF: 0.471 AC: 1635 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.1
DANN	Benign	0.49
PhyloP100		0.10
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: rs2367563; hg19: chr12-96057184;