rs1485608

Positions:

• chr4-95492624-T-A
• chr4-95492624-T-C
• chr4-95492624-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.124+56110A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,026 control chromosomes in the GnomAD database, including 10,680 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 0.36 (10680 hom., cov: 32)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC5C	NM_003728.4	c.124+56110A>T		intron_variant		ENST00000453304.6
UNC5C	XM_005263321.4	c.124+56110A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC5C	ENST00000453304.6	c.124+56110A>T		intron_variant		1	NM_003728.4	P1
UNC5C	ENST00000506749.5	c.124+56110A>T		intron_variant		1
UNC5C	ENST00000513796.5	c.124+56110A>T		intron_variant		1
UNC5C	ENST00000504962.1	c.124+56110A>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54041 AN: 150908 Hom.: 10684 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.358 AC: 54040 AN: 151026 Hom.: 10680 Cov.: 32 AF XY: 0.362 AC XY: 26701 AN XY: 73738

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.453

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.368

Alfa AF: 0.254 Hom.: 700

Bravo AF: 0.343

Asia WGS AF: 0.443 AC: 1534 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.4
DANN	Benign	0.79

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: rs1485608; hg19: chr4-96413775;