4-95242093-A-G

Variant names:

• chr4-95242093-A-G
• rs11730446
• NM_003728.4:c.1108+336T>C

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+336T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,916 control chromosomes in the GnomAD database, including 14,243 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 0.43 (14243 hom., cov: 32)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.915
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC5C	NM_003728.4	MANE Select	c.1108+336T>C		intron	N/A	NP_003719.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC5C	ENST00000453304.6	TSL:1 MANE Select	c.1108+336T>C		intron	N/A	ENSP00000406022.1
	UNC5C	ENST00000513796.5	TSL:1	c.1108+336T>C		intron	N/A	ENSP00000426924.1
	UNC5C	ENST00000506749.5	TSL:1	c.1108+336T>C		intron	N/A	ENSP00000426153.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65005 AN: 151798 Hom.: 14208 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.429 AC: 65105 AN: 151916 Hom.: 14243 Cov.: 32 AF XY: 0.436 AC XY: 32339 AN XY: 74226

African (AFR) AF: 0.438 AC: 18147 AN: 41406

American (AMR) AF: 0.396 AC: 6044 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1225 AN: 3470

East Asian (EAS) AF: 0.620 AC: 3180 AN: 5130

South Asian (SAS) AF: 0.559 AC: 2689 AN: 4814

European-Finnish (FIN) AF: 0.487 AC: 5147 AN: 10562

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27336 AN: 67946

Other (OTH) AF: 0.391 AC: 824 AN: 2106

Alfa AF: 0.401 Hom.: 20758

Bravo AF: 0.420

Asia WGS AF: 0.583 AC: 2028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.56
DANN	Benign	0.56
PhyloP100		-0.92
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: rs11730446; hg19: chr4-96163244;