rs2001246

Positions:

• chr4-95242184-A-T

Variant summary

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

The NM_003728.4(UNC5C):​c.1108+245T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,208 control chromosomes in the GnomAD database, including 2,151 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 (2151 hom., cov: 33)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC5C	NM_003728.4	c.1108+245T>A		intron_variant		ENST00000453304.6
UNC5C	XM_005263321.4	c.1108+245T>A		intron_variant
UNC5C	XM_047416345.1	c.7+245T>A		intron_variant
UNC5C	XM_047416346.1	c.7+245T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC5C	ENST00000453304.6	c.1108+245T>A		intron_variant		1	NM_003728.4	P1
UNC5C	ENST00000506749.5	c.1108+245T>A		intron_variant		1
UNC5C	ENST00000513796.5	c.1108+245T>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20792 AN: 152090 Hom.: 2129 Cov.: 33

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0848

Gnomad ASJ AF: 0.0593

Gnomad EAS AF: 0.0119

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.0857

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0788

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.137 AC: 20864 AN: 152208 Hom.: 2151 Cov.: 33 AF XY: 0.137 AC XY: 10221 AN XY: 74452

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.0846

Gnomad4 ASJ AF: 0.0593

Gnomad4 EAS AF: 0.0120

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.0857

Gnomad4 NFE AF: 0.0788

Gnomad4 OTH AF: 0.133

Alfa AF: 0.112 Hom.: 199

Bravo AF: 0.140

Asia WGS AF: 0.126 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.61

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: rs2001246; hg19: chr4-96163335; COSMIC: COSV71660695;