rs3775045

Variant names:

• chr4-95205733-T-C
• rs3775045
• NM_003728.4:c.1902+895A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003728.4(UNC5C):​c.1902+895A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 151,974 control chromosomes in the GnomAD database, including 42,940 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 0.74 (42940 hom., cov: 31)
• Consequence: UNC5C NM_003728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.875
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC5C	NM_003728.4	c.1902+895A>G		intron_variant	Intron 11 of 15	ENST00000453304.6	NP_003719.3
UNC5C	XM_005263321.4	c.1959+895A>G		intron_variant	Intron 12 of 16		XP_005263378.1
UNC5C	XM_047416345.1	c.858+895A>G		intron_variant	Intron 13 of 17		XP_047272301.1
UNC5C	XM_047416346.1	c.858+895A>G		intron_variant	Intron 14 of 18		XP_047272302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC5C	ENST00000453304.6	c.1902+895A>G		intron_variant	Intron 11 of 15	1	NM_003728.4	ENSP00000406022.1
UNC5C	ENST00000513796.5	c.1959+895A>G		intron_variant	Intron 12 of 13	1		ENSP00000426924.1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112891 AN: 151856 Hom.: 42920 Cov.: 31

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.871

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.902

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.743 AC: 112957 AN: 151974 Hom.: 42940 Cov.: 31 AF XY: 0.734 AC XY: 54508 AN XY: 74278

African (AFR) AF: 0.690 AC: 28561 AN: 41420

American (AMR) AF: 0.673 AC: 10266 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.902 AC: 3130 AN: 3470

East Asian (EAS) AF: 0.331 AC: 1707 AN: 5162

South Asian (SAS) AF: 0.696 AC: 3355 AN: 4820

European-Finnish (FIN) AF: 0.723 AC: 7613 AN: 10526

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55583 AN: 67996

Other (OTH) AF: 0.797 AC: 1682 AN: 2110

Alfa AF: 0.791 Hom.: 150109

Bravo AF: 0.734

Asia WGS AF: 0.523 AC: 1816 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.28
DANN	Benign	0.50
PhyloP100		-0.88
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: rs3775045; hg19: chr4-96126884;