rs4444836

Positions:

• chr4-95467500-A-G

Variant summary

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

The NM_003728.4(UNC5C):​c.124+81234T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,094 control chromosomes in the GnomAD database, including 4,233 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 0.22 (4233 hom., cov: 32)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC5C	NM_003728.4	c.124+81234T>C		intron_variant		ENST00000453304.6	NP_003719.3
UNC5C	XM_005263321.4	c.124+81234T>C		intron_variant			XP_005263378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC5C	ENST00000453304.6	c.124+81234T>C		intron_variant		1	NM_003728.4	ENSP00000406022	P1
UNC5C	ENST00000506749.5	c.124+81234T>C		intron_variant		1		ENSP00000426153
UNC5C	ENST00000513796.5	c.124+81234T>C		intron_variant		1		ENSP00000426924
UNC5C	ENST00000504962.1	c.124+81234T>C		intron_variant		2		ENSP00000425117

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32945 AN: 151976 Hom.: 4226 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.217 AC: 32971 AN: 152094 Hom.: 4233 Cov.: 32 AF XY: 0.217 AC XY: 16154 AN XY: 74344

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.216

Alfa AF: 0.169 Hom.: 3152

Bravo AF: 0.227

Asia WGS AF: 0.359 AC: 1246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.47

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: rs4444836; hg19: chr4-96388651;