rs13120458

Variant names:

• chr4-95243703-A-T
• rs13120458
• NM_003728.4:c.944-1110T>A

Variant summary

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

The NM_003728.4(UNC5C):​c.944-1110T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,190 control chromosomes in the GnomAD database, including 2,377 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 0.16 (2377 hom., cov: 32)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.80
• Publications: 1 publications found

Genes affected

UNC5C (HGNC:12569): (unc-5 netrin receptor C) This gene product belongs to the UNC-5 family of netrin receptors. Netrins are secreted proteins that direct axon extension and cell migration during neural development. They are bifunctional proteins that act as attractants for some cell types and as repellents for others, and these opposite actions are thought to be mediated by two classes of receptors. The UNC-5 family of receptors mediate the repellent response to netrin; they are transmembrane proteins containing 2 immunoglobulin (Ig)-like domains and 2 type I thrombospondin motifs in the extracellular region. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003728.4. 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
	UNC5C	NM_003728.4	MANE Select	c.944-1110T>A		intron	N/A	NP_003719.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC5C	ENST00000453304.6	TSL:1 MANE Select	c.944-1110T>A		intron	N/A	ENSP00000406022.1
	UNC5C	ENST00000513796.5	TSL:1	c.944-1110T>A		intron	N/A	ENSP00000426924.1
	UNC5C	ENST00000506749.5	TSL:1	c.944-1110T>A		intron	N/A	ENSP00000426153.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23853 AN: 152072 Hom.: 2375 Cov.: 32

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.157 AC: 23859 AN: 152190 Hom.: 2377 Cov.: 32 AF XY: 0.157 AC XY: 11708 AN XY: 74402

African (AFR) AF: 0.0393 AC: 1632 AN: 41558

American (AMR) AF: 0.119 AC: 1815 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3470

East Asian (EAS) AF: 0.261 AC: 1350 AN: 5172

South Asian (SAS) AF: 0.270 AC: 1305 AN: 4828

European-Finnish (FIN) AF: 0.202 AC: 2130 AN: 10564

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14454 AN: 67986

Other (OTH) AF: 0.158 AC: 334 AN: 2114

Alfa AF: 0.176 Hom.: 352

Bravo AF: 0.145

Asia WGS AF: 0.236 AC: 820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.8
DANN	Benign	0.68
PhyloP100		2.8
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: rs13120458; hg19: chr4-96164854;