rs13120458

chr4-95243703-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC5C	NM_003728.4	c.944-1110T>A		intron_variant		ENST00000453304.6
UNC5C	XM_005263321.4	c.944-1110T>A		intron_variant
UNC5C	XM_047416345.1	c.-158-1110T>A		intron_variant
UNC5C	XM_047416346.1	c.-158-1110T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC5C	ENST00000453304.6	c.944-1110T>A		intron_variant		1	NM_003728.4	P1
UNC5C	ENST00000506749.5	c.944-1110T>A		intron_variant		1
UNC5C	ENST00000513796.5	c.944-1110T>A		intron_variant		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

Gnomad4 AFR AF: 0.0393

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.158

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	8.8
Dann	Benign	0.68

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: rs13120458; hg19: chr4-96164854;