rs72672784

Positions:

• chr4-95239105-T-C

Variant summary

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

The NM_003728.4(UNC5C):​c.1108+3324A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0327 in 152,304 control chromosomes in the GnomAD database, including 108 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 0.033 (108 hom., cov: 33)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.76

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC5C	NM_003728.4	c.1108+3324A>G		intron_variant		ENST00000453304.6	NP_003719.3
UNC5C	XM_005263321.4	c.1108+3324A>G		intron_variant			XP_005263378.1
UNC5C	XM_047416345.1	c.7+3324A>G		intron_variant			XP_047272301.1
UNC5C	XM_047416346.1	c.7+3324A>G		intron_variant			XP_047272302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC5C	ENST00000453304.6	c.1108+3324A>G		intron_variant		1	NM_003728.4	ENSP00000406022	P1
UNC5C	ENST00000506749.5	c.1108+3324A>G		intron_variant		1		ENSP00000426153
UNC5C	ENST00000513796.5	c.1108+3324A>G		intron_variant		1		ENSP00000426924

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 4959 AN: 152186 Hom.: 105 Cov.: 33

Gnomad AFR AF: 0.00953

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0316

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0857

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0427

Gnomad OTH AF: 0.0353

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

GnomAD4 genome AF: 0.0327 AC: 4975 AN: 152304 Hom.: 108 Cov.: 33 AF XY: 0.0334 AC XY: 2486 AN XY: 74478

Gnomad4 AFR AF: 0.00957

Gnomad4 AMR AF: 0.0316

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.0860

Gnomad4 FIN AF: 0.0369

Gnomad4 NFE AF: 0.0427

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0396 Hom.: 27

Bravo AF: 0.0297

Asia WGS AF: 0.0560 AC: 194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.051
DANN	Benign	0.82

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: rs72672784; hg19: chr4-96160256;