rs2626053

Positions:

• chr4-95333937-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003728.4(UNC5C):​c.346+1473C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 151,954 control chromosomes in the GnomAD database, including 2,087 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 0.16 (2087 hom., cov: 31)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC5C	NM_003728.4	c.346+1473C>T		intron_variant		ENST00000453304.6	NP_003719.3
UNC5C	XM_005263321.4	c.346+1473C>T		intron_variant			XP_005263378.1
UNC5C	XM_047416345.1	c.-756+1473C>T		intron_variant			XP_047272301.1
UNC5C	XM_047416346.1	c.-756+1473C>T		intron_variant			XP_047272302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC5C	ENST00000453304.6	c.346+1473C>T		intron_variant		1	NM_003728.4	ENSP00000406022	P1
UNC5C	ENST00000506749.5	c.346+1473C>T		intron_variant		1		ENSP00000426153
UNC5C	ENST00000513796.5	c.346+1473C>T		intron_variant		1		ENSP00000426924
UNC5C	ENST00000504962.1	c.346+1473C>T		intron_variant		2		ENSP00000425117

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23885 AN: 151836 Hom.: 2087 Cov.: 31

Gnomad AFR AF: 0.0927

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.157 AC: 23891 AN: 151954 Hom.: 2087 Cov.: 31 AF XY: 0.159 AC XY: 11844 AN XY: 74266

Gnomad4 AFR AF: 0.0928

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.147

Alfa AF: 0.174 Hom.: 4897

Bravo AF: 0.153

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
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: rs2626053; hg19: chr4-96255088;