rs12643654

Variant names:

• chr4-95238666-A-G
• rs12643654
• NM_003728.4:c.1108+3763T>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+3763T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 152,174 control chromosomes in the GnomAD database, including 590 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 0.078 (590 hom., cov: 33)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 10 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC5C	NM_003728.4	c.1108+3763T>C		intron_variant	Intron 7 of 15	ENST00000453304.6	NP_003719.3
UNC5C	XM_005263321.4	c.1108+3763T>C		intron_variant	Intron 7 of 16		XP_005263378.1
UNC5C	XM_047416345.1	c.7+3763T>C		intron_variant	Intron 8 of 17		XP_047272301.1
UNC5C	XM_047416346.1	c.7+3763T>C		intron_variant	Intron 9 of 18		XP_047272302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC5C	ENST00000453304.6	c.1108+3763T>C		intron_variant	Intron 7 of 15	1	NM_003728.4	ENSP00000406022.1
UNC5C	ENST00000513796.5	c.1108+3763T>C		intron_variant	Intron 7 of 13	1		ENSP00000426924.1
UNC5C	ENST00000506749.5	c.1108+3763T>C		intron_variant	Intron 7 of 10	1		ENSP00000426153.1

Frequencies

GnomAD3 genomes AF: 0.0778 AC: 11827 AN: 152054 Hom.: 591 Cov.: 33

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0718

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.0549

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.0996

Gnomad OTH AF: 0.0847

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

GnomAD4 genome AF: 0.0777 AC: 11828 AN: 152174 Hom.: 590 Cov.: 33 AF XY: 0.0777 AC XY: 5779 AN XY: 74402

African (AFR) AF: 0.0175 AC: 729 AN: 41568

American (AMR) AF: 0.0716 AC: 1094 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3472

East Asian (EAS) AF: 0.163 AC: 845 AN: 5174

South Asian (SAS) AF: 0.0553 AC: 267 AN: 4826

European-Finnish (FIN) AF: 0.118 AC: 1252 AN: 10580

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0997 AC: 6773 AN: 67956

Other (OTH) AF: 0.0862 AC: 182 AN: 2112

Alfa AF: 0.0981 Hom.: 1791

Bravo AF: 0.0719

Asia WGS AF: 0.0940 AC: 326 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.75
PhyloP100		1.5
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: rs12643654; hg19: chr4-96159817;