chr4-95178216-C-T

Position:

• chr4-95178216-C-T

Variant summary

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

The NM_003728.4(UNC5C):​c.2451+4681G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,084 control chromosomes in the GnomAD database, including 17,265 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 0.45 (17265 hom., cov: 32)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.784

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC5C	NM_003728.4	c.2451+4681G>A		intron_variant		ENST00000453304.6
UNC5C	XM_005263321.4	c.2508+4681G>A		intron_variant
UNC5C	XM_047416345.1	c.1407+4681G>A		intron_variant
UNC5C	XM_047416346.1	c.1407+4681G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC5C	ENST00000453304.6	c.2451+4681G>A		intron_variant		1	NM_003728.4	P1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68562 AN: 151966 Hom.: 17261 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.451 AC: 68598 AN: 152084 Hom.: 17265 Cov.: 32 AF XY: 0.453 AC XY: 33670 AN XY: 74344

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.483

Alfa AF: 0.494 Hom.: 3783

Bravo AF: 0.448

Asia WGS AF: 0.337 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.12
DANN	Benign	0.48

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: rs11097458; hg19: chr4-96099367;