rs2241743

chr4-95170373-G-Achr4-95170373-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003728.4(UNC5C):c.2452-41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,596,656 control chromosomes in the GnomAD database, including 253,923 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 0.56 (24194 hom., cov: 33)
  • Exomes 𝑓: 0.56 (229729 hom.)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC5C	NM_003728.4	c.2452-41C>T		intron_variant		ENST00000453304.6
UNC5C	XM_005263321.4	c.2509-41C>T		intron_variant
UNC5C	XM_047416345.1	c.1408-41C>T		intron_variant
UNC5C	XM_047416346.1	c.1408-41C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC5C	ENST00000453304.6	c.2452-41C>T		intron_variant		1	NM_003728.4	P1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85190 AN: 151924 Hom.: 24168 Cov.: 33

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.576

GnomAD3 exomes AF: 0.554 AC: 135578 AN: 244652 Hom.: 39002 AF XY: 0.543 AC XY: 71725 AN XY: 132140

Gnomad AFR exome AF: 0.539

Gnomad AMR exome AF: 0.699

Gnomad ASJ exome AF: 0.667

Gnomad EAS exome AF: 0.350

Gnomad SAS exome AF: 0.372

Gnomad FIN exome AF: 0.609

Gnomad NFE exome AF: 0.572

Gnomad OTH exome AF: 0.590

GnomAD4 exome AF: 0.560 AC: 808573 AN: 1444614 Hom.: 229729 Cov.: 31 AF XY: 0.554 AC XY: 396492 AN XY: 715630

Gnomad4 AFR exome AF: 0.551

Gnomad4 AMR exome AF: 0.692

Gnomad4 ASJ exome AF: 0.661

Gnomad4 EAS exome AF: 0.357

Gnomad4 SAS exome AF: 0.371

Gnomad4 FIN exome AF: 0.599

Gnomad4 NFE exome AF: 0.572

Gnomad4 OTH exome AF: 0.558

GnomAD4 genome AF: 0.561 AC: 85267 AN: 152042 Hom.: 24194 Cov.: 33 AF XY: 0.559 AC XY: 41555 AN XY: 74298

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.572

Alfa AF: 0.577 Hom.: 6425

Bravo AF: 0.569

Asia WGS AF: 0.372 AC: 1298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.3
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

Other links and lift over

dbSNP: rs2241743; hg19: chr4-96091524; COSMIC: COSV71660260;