4-95178216-C-T

Variant names:

• chr4-95178216-C-T
• rs11097458
• NM_003728.4:c.2451+4681G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.88).
• 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 rank	MANE	Protein	UniProt
UNC5C	NM_003728.4	c.2451+4681G>A		intron_variant	Intron 14 of 15	ENST00000453304.6	NP_003719.3
UNC5C	XM_005263321.4	c.2508+4681G>A		intron_variant	Intron 15 of 16		XP_005263378.1
UNC5C	XM_047416345.1	c.1407+4681G>A		intron_variant	Intron 16 of 17		XP_047272301.1
UNC5C	XM_047416346.1	c.1407+4681G>A		intron_variant	Intron 17 of 18		XP_047272302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC5C	ENST00000453304.6	c.2451+4681G>A		intron_variant	Intron 14 of 15	1	NM_003728.4	ENSP00000406022.1

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

African (AFR) AF: 0.223 AC: 9247 AN: 41486

American (AMR) AF: 0.589 AC: 9004 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2077 AN: 3472

East Asian (EAS) AF: 0.357 AC: 1839 AN: 5148

South Asian (SAS) AF: 0.340 AC: 1640 AN: 4828

European-Finnish (FIN) AF: 0.580 AC: 6135 AN: 10574

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 37008 AN: 67968

Other (OTH) AF: 0.483 AC: 1022 AN: 2114

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
PhyloP100		-0.78
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: rs11097458; hg19: chr4-96099367;