rs9358799

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000562221.1(ENSG00000282804):​c.*6+1G>T variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,375,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

ENSG00000282804
ENST00000562221.1 splice_donor, intron

Scores

2
Splicing: ADA: 0.01195
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.390
Variant links:
Genes affected
RIPOR2 (HGNC:13872): (RHO family interacting cell polarization regulator 2) This gene encodes an atypical inhibitor of the small G protein RhoA. Inhibition of RhoA activity by the encoded protein mediates myoblast fusion and polarization of T cells and neutrophils. The encoded protein is a component of hair cell stereocilia that is essential for hearing. A splice site mutation in this gene results in hearing loss in human patients. [provided by RefSeq, Sep 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RIPOR2NM_001286445.3 linkc.*7G>T 3_prime_UTR_variant Exon 22 of 22 ENST00000643898.2 NP_001273374.1 A0A2R8YEE0B7Z5J9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RIPOR2ENST00000643898 linkc.*7G>T 3_prime_UTR_variant Exon 22 of 22 NM_001286445.3 ENSP00000494268.2 A0A2R8YEE0
ENSG00000282804ENST00000562221.1 linkc.*6+1G>T splice_donor_variant, intron_variant Intron 2 of 2 5 ENSP00000455145.1 H3BP45

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.27e-7
AC:
1
AN:
1375866
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
679908
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.45e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.62
CADD
Benign
9.9
DANN
Benign
0.95

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.012
dbscSNV1_RF
Benign
0.14
SpliceAI score (max)
0.93
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.93
Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-24806594; API