rs692843

Positions:

• chr5-176828645-G-A

Variant summary

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

The NM_133369.3(UNC5A):​c.70+17825G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 152,202 control chromosomes in the GnomAD database, including 49,725 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 0.75 (49725 hom., cov: 33)
• Consequence: UNC5A NM_133369.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.779

Genes affected

UNC5A (HGNC:12567): (unc-5 netrin receptor A) UNC5A belongs to a family of netrin-1 (MIM 601614) receptors thought to mediate the chemorepulsive effect of netrin-1 on specific axons. For more information on UNC5 proteins, see UNC5C (MIM 603610).[supplied by OMIM, Apr 2004]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC5A	NM_133369.3	c.70+17825G>A		intron_variant		ENST00000329542.9	NP_588610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC5A	ENST00000329542.9	c.70+17825G>A		intron_variant		1	NM_133369.3	ENSP00000332737
UNC5A	ENST00000509580.2	c.70+17825G>A		intron_variant		5		ENSP00000421795	P1

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114482 AN: 152084 Hom.: 49727 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.910

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.946

Gnomad OTH AF: 0.785

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.752 AC: 114490 AN: 152202 Hom.: 49725 Cov.: 33 AF XY: 0.761 AC XY: 56621 AN XY: 74430

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.848

Gnomad4 ASJ AF: 0.918

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.911

Gnomad4 FIN AF: 0.994

Gnomad4 NFE AF: 0.946

Gnomad4 OTH AF: 0.784

Alfa AF: 0.908 Hom.: 106736

Bravo AF: 0.716

Asia WGS AF: 0.851 AC: 2959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.057
DANN	Benign	0.48

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: rs692843; hg19: chr5-176255646;