NM_001286445.3:c.447+809A>C

Variant names:

• chr6-24870057-T-G
• rs1884160
• NM_001286445.3:c.447+809A>C

Variant summary

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

The NM_001286445.3(RIPOR2):​c.447+809A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,022 control chromosomes in the GnomAD database, including 13,140 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 0.41 (13140 hom., cov: 33)
• Consequence: RIPOR2 NM_001286445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475

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]

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 (AFR) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPOR2	NM_001286445.3	c.447+809A>C		intron_variant	Intron 5 of 21	ENST00000643898.2	NP_001273374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPOR2	ENST00000643898.2	c.447+809A>C		intron_variant	Intron 5 of 21		NM_001286445.3	ENSP00000494268.2

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61601 AN: 151904 Hom.: 13126 Cov.: 33

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.406 AC: 61662 AN: 152022 Hom.: 13140 Cov.: 33 AF XY: 0.402 AC XY: 29904 AN XY: 74324

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.367

Alfa AF: 0.215 Hom.: 446

Bravo AF: 0.413

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.58

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: rs1884160; hg19: chr6-24870285;