rs12823

Variant names:

• chr11-124884715-T-A
• rs12823
• ENST00000534407.5:n.3407A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-124884715-T-A
• chr11-124884715-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000534407.5(ROBO4):​n.3407A>T variant causes a non coding transcript exon 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 ENST00000534407.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360
• Publications: 14 publications found

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]

ROBO4 Gene-Disease associations (from GenCC):

• aortic valve disease 3

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia

ENSG00000254568 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000534407.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO4	NM_019055.6	MANE Select	c.*176A>T		3_prime_UTR	Exon 18 of 18	NP_061928.4
	ROBO4	NM_001441183.1		c.*176A>T		3_prime_UTR	Exon 18 of 18	NP_001428112.1
	ROBO4	NM_001301088.2		c.*176A>T		3_prime_UTR	Exon 18 of 18	NP_001288017.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROBO4	ENST00000534407.5	TSL:1	n.3407A>T		non_coding_transcript_exon	Exon 5 of 5
	ROBO4	ENST00000306534.8	TSL:1 MANE Select	c.*176A>T		3_prime_UTR	Exon 18 of 18	ENSP00000304945.3
	ROBO4	ENST00000533054.5	TSL:2	c.*176A>T		3_prime_UTR	Exon 18 of 18	ENSP00000437129.1

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

African (AFR) AF: 0.220 AC: 3331 AN: 15114

American (AMR) AF: 0.189 AC: 4807 AN: 25412

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 3981 AN: 15302

East Asian (EAS) AF: 0.000558 AC: 19 AN: 34026

South Asian (SAS) AF: 0.128 AC: 6631 AN: 51914

European-Finnish (FIN) AF: 0.351 AC: 16024 AN: 45642

Middle Eastern (MID) AF: 0.266 AC: 633 AN: 2382

European-Non Finnish (NFE) AF: 0.379 AC: 133508 AN: 352480

Other (OTH) AF: 0.309 AC: 9418 AN: 30444

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

African (AFR) AF: 0.221 AC: 9186 AN: 41500

American (AMR) AF: 0.238 AC: 3644 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 929 AN: 3470

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5172

South Asian (SAS) AF: 0.126 AC: 610 AN: 4828

European-Finnish (FIN) AF: 0.341 AC: 3612 AN: 10582

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25495 AN: 67982

Other (OTH) AF: 0.295 AC: 623 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.75
PhyloP100		-0.036
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: rs12823; hg19: chr11-124754611;