rs12823

Positions:

• chr11-124884715-T-A

Variant summary

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

The NM_019055.6(ROBO4):​c.*176A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 724,856 control chromosomes in the GnomAD database, including 38,781 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 0.29 (7151 hom., cov: 32)
  • Exomes 𝑓: 0.31 (31630 hom.)
• Consequence: ROBO4 NM_019055.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360

Genes affected

ROBO4 (HGNC:17985): (roundabout guidance receptor 4) Predicted to enable cell-cell adhesion mediator activity. Involved in angiogenesis and establishment of endothelial barrier. Located in extracellular exosome. Implicated in aortic valve disease 3. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROBO4	NM_019055.6	c.*176A>T		3_prime_UTR_variant	18/18	ENST00000306534.8	NP_061928.4
ROBO4	NM_001301088.2	c.*176A>T		3_prime_UTR_variant	18/18		NP_001288017.1
ROBO4	XM_006718861.3	c.*176A>T		3_prime_UTR_variant	18/18		XP_006718924.1
ROBO4	XM_011542875.2	c.*176A>T		3_prime_UTR_variant	11/11		XP_011541177.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROBO4	ENST00000306534.8	c.*176A>T		3_prime_UTR_variant	18/18	1	NM_019055.6	ENSP00000304945	P1
ROBO4	ENST00000534407.5	n.3407A>T		non_coding_transcript_exon_variant	5/5	1
	ENST00000524453.1	n.673+352T>A		intron_variant, non_coding_transcript_variant		3
ROBO4	ENST00000533054.5	c.*176A>T		3_prime_UTR_variant	18/18	2		ENSP00000437129

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44446 AN: 152022 Hom.: 7157 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.298

GnomAD4 exome AF: 0.311 AC: 178352 AN: 572716 Hom.: 31630 Cov.: 7 AF XY: 0.304 AC XY: 91767 AN XY: 302136

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.000558

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.379

Gnomad4 OTH exome AF: 0.309

GnomAD4 genome AF: 0.292 AC: 44438 AN: 152140 Hom.: 7151 Cov.: 32 AF XY: 0.285 AC XY: 21185 AN XY: 74388

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.295

Alfa AF: 0.337 Hom.: 1209

Bravo AF: 0.282

Asia WGS AF: 0.0660 AC: 230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.75

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: rs12823; hg19: chr11-124754611;