rs3740462

Positions:

• chr10-71291226-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_170744.5(UNC5B):​c.1294+117C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 1,385,456 control chromosomes in the GnomAD database, including 419,607 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 0.69 (38163 hom., cov: 30)
  • Exomes 𝑓: 0.78 (381444 hom.)
• Consequence: UNC5B NM_170744.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC5B	NM_170744.5	c.1294+117C>T		intron_variant		ENST00000335350.10	NP_734465.2
UNC5B	NM_001244889.2	c.1261+117C>T		intron_variant			NP_001231818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC5B	ENST00000335350.10	c.1294+117C>T		intron_variant		1	NM_170744.5	ENSP00000334329	P4
UNC5B	ENST00000373192.4	c.1261+117C>T		intron_variant		1		ENSP00000362288	A1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104664 AN: 151786 Hom.: 38164 Cov.: 30

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.736

GnomAD4 exome AF: 0.783 AC: 966348 AN: 1233552 Hom.: 381444 AF XY: 0.783 AC XY: 478521 AN XY: 610770

Gnomad4 AFR exome AF: 0.426

Gnomad4 AMR exome AF: 0.786

Gnomad4 ASJ exome AF: 0.731

Gnomad4 EAS exome AF: 0.671

Gnomad4 SAS exome AF: 0.727

Gnomad4 FIN exome AF: 0.789

Gnomad4 NFE exome AF: 0.804

Gnomad4 OTH exome AF: 0.758

GnomAD4 genome AF: 0.689 AC: 104699 AN: 151904 Hom.: 38163 Cov.: 30 AF XY: 0.694 AC XY: 51520 AN XY: 74262

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.774

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.798

Gnomad4 NFE AF: 0.805

Gnomad4 OTH AF: 0.734

Alfa AF: 0.773 Hom.: 20935

Bravo AF: 0.676

Asia WGS AF: 0.662 AC: 2303 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs3740462; hg19: chr10-73050983; COSMIC: COSV58977338;