4-95546352-C-T

Variant names:

• chr4-95546352-C-T
• rs11097470
• NM_003728.4:c.124+2382G>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.124+2382G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,138 control chromosomes in the GnomAD database, including 1,478 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 0.13 (1478 hom., cov: 32)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• Publications: 13 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC5C	NM_003728.4	c.124+2382G>A		intron_variant	Intron 1 of 15	ENST00000453304.6	NP_003719.3
UNC5C	XM_005263321.4	c.124+2382G>A		intron_variant	Intron 1 of 16		XP_005263378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC5C	ENST00000453304.6	c.124+2382G>A		intron_variant	Intron 1 of 15	1	NM_003728.4	ENSP00000406022.1
UNC5C	ENST00000513796.5	c.124+2382G>A		intron_variant	Intron 1 of 13	1		ENSP00000426924.1
UNC5C	ENST00000506749.5	c.124+2382G>A		intron_variant	Intron 1 of 10	1		ENSP00000426153.1
UNC5C	ENST00000504962.1	c.124+2382G>A		intron_variant	Intron 1 of 5	2		ENSP00000425117.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20428 AN: 152020 Hom.: 1480 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.0972

Gnomad ASJ AF: 0.0908

Gnomad EAS AF: 0.0571

Gnomad SAS AF: 0.0456

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.134 AC: 20447 AN: 152138 Hom.: 1478 Cov.: 32 AF XY: 0.131 AC XY: 9751 AN XY: 74378

African (AFR) AF: 0.173 AC: 7168 AN: 41480

American (AMR) AF: 0.0971 AC: 1485 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0908 AC: 315 AN: 3470

East Asian (EAS) AF: 0.0568 AC: 294 AN: 5174

South Asian (SAS) AF: 0.0460 AC: 222 AN: 4824

European-Finnish (FIN) AF: 0.118 AC: 1254 AN: 10588

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9229 AN: 67992

Other (OTH) AF: 0.126 AC: 266 AN: 2112

Alfa AF: 0.130 Hom.: 3905

Bravo AF: 0.135

Asia WGS AF: 0.0530 AC: 186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.71
DANN	Benign	0.59
PhyloP100		-0.17
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: rs11097470; hg19: chr4-96467503;