rs2001246

Variant names:

• chr4-95242184-A-T
• rs2001246
• NM_003728.4:c.1108+245T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003728.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC5C	NM_003728.4	MANE Select	c.1108+245T>A		intron	N/A	NP_003719.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC5C	ENST00000453304.6	TSL:1 MANE Select	c.1108+245T>A		intron	N/A	ENSP00000406022.1	O95185-1
	UNC5C	ENST00000513796.5	TSL:1	c.1108+245T>A		intron	N/A	ENSP00000426924.1	E0CX15
	UNC5C	ENST00000506749.5	TSL:1	c.1108+245T>A		intron	N/A	ENSP00000426153.1	O95185-2

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

African (AFR) AF: 0.285 AC: 11814 AN: 41484

American (AMR) AF: 0.0846 AC: 1295 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0593 AC: 206 AN: 3472

East Asian (EAS) AF: 0.0120 AC: 62 AN: 5180

South Asian (SAS) AF: 0.174 AC: 840 AN: 4822

European-Finnish (FIN) AF: 0.0857 AC: 910 AN: 10622

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0788 AC: 5359 AN: 68010

Other (OTH) AF: 0.133 AC: 281 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.61
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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