rs546447428

Variant names:

• chr10-71213056-G-C
• rs546447428
• NM_170744.5:c.71G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-71213056-G-C
• chr10-71213056-G-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_170744.5(UNC5B):​c.71G>C​(p.Ser24Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,400,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000088 (0 hom.)
• Consequence: UNC5B NM_170744.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.64
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.043220997).

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.71G>C	p.Ser24Thr	missense	Exon 1 of 17	NP_734465.2
	UNC5B	NM_001244889.2		c.71G>C	p.Ser24Thr	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.71G>C	p.Ser24Thr	missense	Exon 1 of 17	ENSP00000334329.6	Q8IZJ1-1
	UNC5B	ENST00000373192.4	TSL:1	c.71G>C	p.Ser24Thr	missense	Exon 1 of 16	ENSP00000362288.4	Q8IZJ1-2
	UNC5B	ENST00000935474.1		c.71G>C	p.Ser24Thr	missense	Exon 1 of 17	ENSP00000605533.1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000292 AC: 3 AN: 102656 AF XY: 0.00

Gnomad AFR exome AF: 0.000540

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000881 AC: 11 AN: 1248002 Hom.: 0 Cov.: 30 AF XY: 0.00000653 AC XY: 4 AN XY: 612562

African (AFR) AF: 0.000414 AC: 11 AN: 26544

American (AMR) AF: 0.00 AC: 0 AN: 22426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19456

East Asian (EAS) AF: 0.00 AC: 0 AN: 30654

South Asian (SAS) AF: 0.00 AC: 0 AN: 53706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4976

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1001946

Other (OTH) AF: 0.00 AC: 0 AN: 49968

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152282 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74458

African (AFR) AF: 0.000216 AC: 9 AN: 41578

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000132

ExAC AF: 0.0000252 AC: 3

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	0.081
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.45	T
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.6
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.059
Sift	Benign	0.054	T
Sift4G	Benign	0.39	T
Polyphen		0.14	B
Vest4		0.24
MutPred		0.26		Loss of disorder (P = 0.062)
MVP		0.57
MPC		0.15
ClinPred		0.085	T
GERP RS		3.5
PromoterAI		0.013	Neutral
Varity_R		0.089
gMVP		0.27
Mutation Taster		=95/5	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: rs546447428; hg19: chr10-72972813;