rs2367563

chr12-95663408-A-G

Variant summary

Our verdict is Benign. Variant got -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

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:42452): (phosphoglycerate mutase 1 pseudogene 5)

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTN4	NM_021229.4	c.1750+2402T>C		intron_variant		ENST00000343702.9
PGAM1P5	NR_077225.1	n.153-2275A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTN4	ENST00000343702.9	c.1750+2402T>C		intron_variant		1	NM_021229.4	P1
PGAM1P5	ENST00000626376.2	n.220-2275A>G		intron_variant, non_coding_transcript_variant		5

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

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

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.521

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.388

Alfa AF: 0.379 Hom.: 23058

Bravo AF: 0.391

Asia WGS AF: 0.471 AC: 1635 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	6.1
Dann	Benign	0.49

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: rs2367563; hg19: chr12-96057184;