rs763579521

Variant names:

• chr10-71213008-G-C
• rs763579521
• NM_170744.5:c.23G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-71213008-G-C
• chr10-71213008-G-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_170744.5(UNC5B):​c.23G>C​(p.Arg8Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000893 in 1,411,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000087 (0 hom.)
• Consequence: UNC5B NM_170744.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30
• Publications: 0 publications found

Genes affected

UNC5B (HGNC:12568): (unc-5 netrin receptor B) This gene encodes a member of the netrin family of receptors. This particular protein mediates the repulsive effect of netrin-1 and is a vascular netrin receptor. This encoded protein is also in a group of proteins called dependence receptors (DpRs) which are involved in pro- and anti-apoptotic processes. Many DpRs are involved in embryogenesis and in cancer progression. Two alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05580789).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170744.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC5B	NM_170744.5	MANE Select	c.23G>C	p.Arg8Pro	missense	Exon 1 of 17	NP_734465.2
	UNC5B	NM_001244889.2		c.23G>C	p.Arg8Pro	missense	Exon 1 of 16	NP_001231818.1	Q8IZJ1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC5B	ENST00000335350.10	TSL:1 MANE Select	c.23G>C	p.Arg8Pro	missense	Exon 1 of 17	ENSP00000334329.6	Q8IZJ1-1
	UNC5B	ENST00000373192.4	TSL:1	c.23G>C	p.Arg8Pro	missense	Exon 1 of 16	ENSP00000362288.4	Q8IZJ1-2
	UNC5B	ENST00000935474.1		c.23G>C	p.Arg8Pro	missense	Exon 1 of 17	ENSP00000605533.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152032 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.0000816 AC: 9 AN: 110284 AF XY: 0.0000948

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000836

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000944

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000866 AC: 109 AN: 1259232 Hom.: 0 Cov.: 30 AF XY: 0.0000823 AC XY: 51 AN XY: 619660

African (AFR) AF: 0.0000748 AC: 2 AN: 26752

American (AMR) AF: 0.00 AC: 0 AN: 24418

Ashkenazi Jewish (ASJ) AF: 0.000706 AC: 14 AN: 19842

East Asian (EAS) AF: 0.00 AC: 0 AN: 30838

South Asian (SAS) AF: 0.00 AC: 0 AN: 56020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37480

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4736

European-Non Finnish (NFE) AF: 0.0000862 AC: 87 AN: 1008722

Other (OTH) AF: 0.000119 AC: 6 AN: 50424

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152032 Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7 AN XY: 74234

African (AFR) AF: 0.0000483 AC: 2 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67978

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.000189 Hom.: 0

Bravo AF: 0.0000793

ExAC AF: 0.0000593 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.59	T
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.3
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.030	N
REVEL	Benign	0.094
Sift	Benign	0.065	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.35
MVP		0.56
MPC		0.21
ClinPred		0.077	T
GERP RS		0.72
PromoterAI		-0.0036	Neutral
Varity_R		0.38
gMVP		0.53
Mutation Taster		=82/18	polymorphism

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: rs763579521; hg19: chr10-72972765;