4-95452925-T-G

Position:

• chr4-95452925-T-G

Variant summary

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

The NM_003728.4(UNC5C):​c.124+95809A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.715 in 152,136 control chromosomes in the GnomAD database, including 39,475 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 0.72 (39475 hom., cov: 33)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.429

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC5C	NM_003728.4	c.124+95809A>C		intron_variant		ENST00000453304.6	NP_003719.3
UNC5C	XM_005263321.4	c.124+95809A>C		intron_variant			XP_005263378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC5C	ENST00000453304.6	c.124+95809A>C		intron_variant		1	NM_003728.4	ENSP00000406022.1
UNC5C	ENST00000513796.5	c.124+95809A>C		intron_variant		1		ENSP00000426924.1
UNC5C	ENST00000506749.5	c.124+95809A>C		intron_variant		1		ENSP00000426153.1
UNC5C	ENST00000504962.1	c.124+95809A>C		intron_variant		2		ENSP00000425117.1

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108737 AN: 152018 Hom.: 39436 Cov.: 33

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.719

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.715 AC: 108822 AN: 152136 Hom.: 39475 Cov.: 33 AF XY: 0.708 AC XY: 52675 AN XY: 74360

Gnomad4 AFR AF: 0.809

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.741

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.719

Gnomad4 NFE AF: 0.713

Gnomad4 OTH AF: 0.696

Alfa AF: 0.696 Hom.: 17803

Bravo AF: 0.706

Asia WGS AF: 0.579 AC: 2015 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.7
DANN	Benign	0.59

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: rs265045; hg19: chr4-96374076;