rs74690179

Variant names:

• chr4-95251553-C-T
• rs74690179
• NM_003728.4:c.595-886G>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.595-886G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 152,298 control chromosomes in the GnomAD database, including 59 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 0.024 (59 hom., cov: 32)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.075 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC5C	NM_003728.4	c.595-886G>A		intron_variant	Intron 4 of 15	ENST00000453304.6	NP_003719.3
UNC5C	XM_005263321.4	c.595-886G>A		intron_variant	Intron 4 of 16		XP_005263378.1
UNC5C	XM_047416345.1	c.-507-886G>A		intron_variant	Intron 5 of 17		XP_047272301.1
UNC5C	XM_047416346.1	c.-507-886G>A		intron_variant	Intron 6 of 18		XP_047272302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC5C	ENST00000453304.6	c.595-886G>A		intron_variant	Intron 4 of 15	1	NM_003728.4	ENSP00000406022.1
UNC5C	ENST00000513796.5	c.595-886G>A		intron_variant	Intron 4 of 13	1		ENSP00000426924.1
UNC5C	ENST00000506749.5	c.595-886G>A		intron_variant	Intron 4 of 10	1		ENSP00000426153.1
UNC5C	ENST00000504962.1	c.595-886G>A		intron_variant	Intron 4 of 5	2		ENSP00000425117.1

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3599 AN: 152180 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0123

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0814

Gnomad FIN AF: 0.0149

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0210

Gnomad OTH AF: 0.0215

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

GnomAD4 genome AF: 0.0238 AC: 3623 AN: 152298 Hom.: 59 Cov.: 32 AF XY: 0.0242 AC XY: 1804 AN XY: 74470

African (AFR) AF: 0.0306 AC: 1273 AN: 41566

American (AMR) AF: 0.0123 AC: 188 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5184

South Asian (SAS) AF: 0.0816 AC: 394 AN: 4826

European-Finnish (FIN) AF: 0.0149 AC: 158 AN: 10604

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0210 AC: 1428 AN: 68026

Other (OTH) AF: 0.0265 AC: 56 AN: 2116

Alfa AF: 0.0234 Hom.: 27

Bravo AF: 0.0229

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.78
DANN	Benign	0.61
PhyloP100		-0.15
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: rs74690179; hg19: chr4-96172704;