rs13116085

Positions:

• chr4-95318381-G-A
• chr4-95318381-G-T

Variant summary

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

The NM_003728.4(UNC5C):​c.347-16632C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,976 control chromosomes in the GnomAD database, including 16,252 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 (16252 hom., cov: 31)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.494

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC5C	NM_003728.4	c.347-16632C>T		intron_variant		ENST00000453304.6	NP_003719.3
UNC5C	XM_005263321.4	c.347-16632C>T		intron_variant			XP_005263378.1
UNC5C	XM_047416345.1	c.-755-16632C>T		intron_variant			XP_047272301.1
UNC5C	XM_047416346.1	c.-755-16632C>T		intron_variant			XP_047272302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC5C	ENST00000453304.6	c.347-16632C>T		intron_variant		1	NM_003728.4	ENSP00000406022	P1
UNC5C	ENST00000506749.5	c.347-16632C>T		intron_variant		1		ENSP00000426153
UNC5C	ENST00000513796.5	c.347-16632C>T		intron_variant		1		ENSP00000426924
UNC5C	ENST00000504962.1	c.347-16632C>T		intron_variant		2		ENSP00000425117

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65479 AN: 151858 Hom.: 16243 Cov.: 31

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.581

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.431 AC: 65506 AN: 151976 Hom.: 16252 Cov.: 31 AF XY: 0.435 AC XY: 32279 AN XY: 74272

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.828

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.465

Alfa AF: 0.346 Hom.: 1070

Bravo AF: 0.425

Asia WGS AF: 0.669 AC: 2324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.8
DANN	Benign	0.76

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: rs13116085; hg19: chr4-96239532;