6-24891718-G-T

Variant names:

• chr6-24891718-G-T
• rs1007237
• NM_001286445.3:c.62-15901C>A

Variant summary

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

The NM_001286445.3(RIPOR2):​c.62-15901C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 152,068 control chromosomes in the GnomAD database, including 39,920 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 0.72 (39920 hom., cov: 31)
• Consequence: RIPOR2 NM_001286445.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPOR2	NM_001286445.3	c.62-15901C>A		intron_variant	Intron 1 of 21	ENST00000643898.2	NP_001273374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPOR2	ENST00000643898.2	c.62-15901C>A		intron_variant	Intron 1 of 21		NM_001286445.3	ENSP00000494268.2

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108740 AN: 151950 Hom.: 39863 Cov.: 31

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.716 AC: 108853 AN: 152068 Hom.: 39920 Cov.: 31 AF XY: 0.716 AC XY: 53241 AN XY: 74326

Gnomad4 AFR AF: 0.888

Gnomad4 AMR AF: 0.713

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.608

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.687

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.707

Alfa AF: 0.655 Hom.: 17735

Bravo AF: 0.720

Asia WGS AF: 0.680 AC: 2365 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	0.75
DANN	Benign	0.77

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: rs1007237; hg19: chr6-24891946;