rs3912477

chr4-95440002-T-Cchr4-95440002-T-G

Variant summary

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

The NM_003728.4(UNC5C):c.125-104371A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,224 control chromosomes in the GnomAD database, including 1,876 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 0.14 (1876 hom., cov: 32)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC5C	NM_003728.4	c.125-104371A>G		intron_variant		ENST00000453304.6
UNC5C	XM_005263321.4	c.125-104371A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC5C	ENST00000453304.6	c.125-104371A>G		intron_variant		1	NM_003728.4	P1
UNC5C	ENST00000506749.5	c.125-104371A>G		intron_variant		1
UNC5C	ENST00000513796.5	c.125-104371A>G		intron_variant		1
UNC5C	ENST00000504962.1	c.125-104371A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20575 AN: 152106 Hom.: 1878 Cov.: 32

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0223

Gnomad SAS AF: 0.0563

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.135 AC: 20562 AN: 152224 Hom.: 1876 Cov.: 32 AF XY: 0.133 AC XY: 9869 AN XY: 74428

Gnomad4 AFR AF: 0.0352

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.0224

Gnomad4 SAS AF: 0.0559

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.144

Alfa AF: 0.175 Hom.: 1284

Bravo AF: 0.128

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.99
Dann	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3912477; hg19: chr4-96361153;