rs12643654

Positions:

• chr4-95238666-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.1108+3763T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 152,174 control chromosomes in the GnomAD database, including 590 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 0.078 (590 hom., cov: 33)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC5C	NM_003728.4	c.1108+3763T>C		intron_variant		ENST00000453304.6	NP_003719.3
UNC5C	XM_005263321.4	c.1108+3763T>C		intron_variant			XP_005263378.1
UNC5C	XM_047416345.1	c.7+3763T>C		intron_variant			XP_047272301.1
UNC5C	XM_047416346.1	c.7+3763T>C		intron_variant			XP_047272302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC5C	ENST00000453304.6	c.1108+3763T>C		intron_variant		1	NM_003728.4	ENSP00000406022.1
UNC5C	ENST00000513796.5	c.1108+3763T>C		intron_variant		1		ENSP00000426924.1
UNC5C	ENST00000506749.5	c.1108+3763T>C		intron_variant		1		ENSP00000426153.1

Frequencies

GnomAD3 genomes AF: 0.0778 AC: 11827 AN: 152054 Hom.: 591 Cov.: 33

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0718

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.0549

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.0996

Gnomad OTH AF: 0.0847

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

GnomAD4 genome AF: 0.0777 AC: 11828 AN: 152174 Hom.: 590 Cov.: 33 AF XY: 0.0777 AC XY: 5779 AN XY: 74402

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.0716

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.0553

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.0997

Gnomad4 OTH AF: 0.0862

Alfa AF: 0.102 Hom.: 1366

Bravo AF: 0.0719

Asia WGS AF: 0.0940 AC: 326 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.75

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: rs12643654; hg19: chr4-96159817;