chr4-95440002-T-C

Variant names:

• chr4-95440002-T-C
• rs3912477
• NM_003728.4:c.125-104371A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003728.4(UNC5C):​c.125-104371A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,224 control chromosomes in the GnomAD database, including 1,876 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 (1876 hom., cov: 32)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.199 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.125-104371A>G		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.125-104371A>G		intron	N/A	ENSP00000406022.1	O95185-1
	UNC5C	ENST00000513796.5	TSL:1	c.125-104371A>G		intron	N/A	ENSP00000426924.1	E0CX15
	UNC5C	ENST00000506749.5	TSL:1	c.125-104371A>G		intron	N/A	ENSP00000426153.1	O95185-2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20575 AN: 152106 Hom.: 1878 Cov.: 32

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.0223

Gnomad SAS AF: 0.0563

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.135 AC: 20562 AN: 152224 Hom.: 1876 Cov.: 32 AF XY: 0.133 AC XY: 9869 AN XY: 74428

African (AFR) AF: 0.0352 AC: 1462 AN: 41562

American (AMR) AF: 0.119 AC: 1827 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 594 AN: 3470

East Asian (EAS) AF: 0.0224 AC: 116 AN: 5182

South Asian (SAS) AF: 0.0559 AC: 270 AN: 4830

European-Finnish (FIN) AF: 0.198 AC: 2102 AN: 10596

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13699 AN: 67978

Other (OTH) AF: 0.144 AC: 305 AN: 2114

Alfa AF: 0.176 Hom.: 1421

Bravo AF: 0.128

Asia WGS AF: 0.0360 AC: 126 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.99
DANN	Benign	0.32
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3912477; hg19: chr4-96361153;