10-71280008-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_170744.5(UNC5B):c.267C>T(p.Asn89=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,614,100 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (7 hom.)
• Consequence: UNC5B NM_170744.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.68

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

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 10-71280008-C-T is Benign according to our data. Variant chr10-71280008-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2640564.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.68 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC5B	NM_170744.5	c.267C>T	p.Asn89=	synonymous_variant	2/17	ENST00000335350.10
UNC5B	NM_001244889.2	c.267C>T	p.Asn89=	synonymous_variant	2/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC5B	ENST00000335350.10	c.267C>T	p.Asn89=	synonymous_variant	2/17	1	NM_170744.5	P4
UNC5B	ENST00000373192.4	c.267C>T	p.Asn89=	synonymous_variant	2/16	1		A1

Frequencies

GnomAD3 genomes AF: 0.00145 AC: 221 AN: 152242 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00219

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00117 AC: 294 AN: 251096 Hom.: 0 AF XY: 0.00114 AC XY: 155 AN XY: 135840

Gnomad AFR exome AF: 0.000493

Gnomad AMR exome AF: 0.000752

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000425

Gnomad FIN exome AF: 0.00102

Gnomad NFE exome AF: 0.00194

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.00215 AC: 3149 AN: 1461740 Hom.: 7 Cov.: 32 AF XY: 0.00210 AC XY: 1529 AN XY: 727168

Gnomad4 AFR exome AF: 0.000358

Gnomad4 AMR exome AF: 0.000760

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000383

Gnomad4 FIN exome AF: 0.00113

Gnomad4 NFE exome AF: 0.00258

Gnomad4 OTH exome AF: 0.00225

GnomAD4 genome AF: 0.00145 AC: 221 AN: 152360 Hom.: 1 Cov.: 33 AF XY: 0.00144 AC XY: 107 AN XY: 74514

Gnomad4 AFR AF: 0.000577

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000941

Gnomad4 NFE AF: 0.00219

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00207 Hom.: 0

Bravo AF: 0.00168

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

UNC5B: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	2.6
Dann	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs145277612; hg19: chr10-73039765;