rs3740462

Variant names:

• chr10-71291226-C-T
• rs3740462
• NM_170744.5:c.1294+117C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
UNC5B	NM_170744.5	c.1294+117C>T		intron_variant	Intron 9 of 16	ENST00000335350.10	NP_734465.2
UNC5B	NM_001244889.2	c.1261+117C>T		intron_variant	Intron 8 of 15		NP_001231818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC5B	ENST00000335350.10	c.1294+117C>T		intron_variant	Intron 9 of 16	1	NM_170744.5	ENSP00000334329.6
UNC5B	ENST00000373192.4	c.1261+117C>T		intron_variant	Intron 8 of 15	1		ENSP00000362288.4

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

African (AFR) AF: 0.426 AC: 11763 AN: 27600

American (AMR) AF: 0.786 AC: 23910 AN: 30412

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 14166 AN: 19384

East Asian (EAS) AF: 0.671 AC: 25685 AN: 38300

South Asian (SAS) AF: 0.727 AC: 49269 AN: 67736

European-Finnish (FIN) AF: 0.789 AC: 35924 AN: 45512

Middle Eastern (MID) AF: 0.802 AC: 3938 AN: 4910

European-Non Finnish (NFE) AF: 0.804 AC: 762381 AN: 947802

Other (OTH) AF: 0.758 AC: 39312 AN: 51896

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

African (AFR) AF: 0.436 AC: 18036 AN: 41392

American (AMR) AF: 0.774 AC: 11833 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2500 AN: 3468

East Asian (EAS) AF: 0.646 AC: 3322 AN: 5140

South Asian (SAS) AF: 0.713 AC: 3427 AN: 4806

European-Finnish (FIN) AF: 0.798 AC: 8438 AN: 10574

Middle Eastern (MID) AF: 0.795 AC: 232 AN: 292

European-Non Finnish (NFE) AF: 0.805 AC: 54699 AN: 67924

Other (OTH) AF: 0.734 AC: 1551 AN: 2114

Alfa AF: 0.775 Hom.: 23402

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
PhyloP100		0.26
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: rs3740462; hg19: chr10-73050983; COSMIC: COSV58977338;