4-95537282-T-C

Position:

• chr4-95537282-T-C

Variant summary

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

The ENST00000453304.6(UNC5C):​c.124+11452A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,070 control chromosomes in the GnomAD database, including 36,838 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 0.69 (36838 hom., cov: 32)
• Consequence: UNC5C ENST00000453304.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC5C	NM_003728.4	c.124+11452A>G		intron_variant		ENST00000453304.6	NP_003719.3
UNC5C	XM_005263321.4	c.124+11452A>G		intron_variant			XP_005263378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC5C	ENST00000453304.6	c.124+11452A>G		intron_variant		1	NM_003728.4	ENSP00000406022	P1
UNC5C	ENST00000506749.5	c.124+11452A>G		intron_variant		1		ENSP00000426153
UNC5C	ENST00000513796.5	c.124+11452A>G		intron_variant		1		ENSP00000426924
UNC5C	ENST00000504962.1	c.124+11452A>G		intron_variant		2		ENSP00000425117

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105199 AN: 151954 Hom.: 36821 Cov.: 32

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.692 AC: 105264 AN: 152070 Hom.: 36838 Cov.: 32 AF XY: 0.693 AC XY: 51513 AN XY: 74328

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.739

Gnomad4 SAS AF: 0.683

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.726

Alfa AF: 0.671 Hom.: 61630

Bravo AF: 0.707

Asia WGS AF: 0.727 AC: 2532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	12
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10032931; hg19: chr4-96458433;