rs10411210

Variant names:

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_033103.5(RHPN2):c.185+2855G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.213 (AC=32,430) in the gnomAD database across 152,116 control chromosomes, including 5,003 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.421. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 5003 hom., cov: 32)

Consequence

RHPN2
NM_033103.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.73

Publications

157 publications found

Variant links:

Genes affected

RHPN2 (HGNC:19974): (rhophilin Rho GTPase binding protein 2) This gene encodes a member of the rhophilin family of Ras-homologous (Rho)-GTPase binding proteins. The encoded protein binds both GTP- and GDP-bound RhoA and GTP-bound RhoB and may be involved in the organization of the actin cytoskeleton. [provided by RefSeq, Apr 2009]

RHPN2 links:

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new If you want to explore the variant's impact on the transcript NM_033103.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -12 points.

Show applied only (2)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.4211 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_033103.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHPN2	NM_033103.5	MANE Select	c.185+2855G>A		intron	N/A	NP_149094.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RHPN2	ENST00000254260.8	TSL:1 MANE Select	c.185+2855G>A	intron	N/A	ENSP00000254260.2	Q8IUC4-1
RHPN2	ENST00000859930.1		c.185+2855G>A	intron	N/A	ENSP00000529989.1	A0ACI8RL70
RHPN2	ENST00000588388.5	TSL:2	n.185+2855G>A	intron	N/A	ENSP00000465898.1	K7EL35

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.213	AC:32348	Hom:4972	AN:151998	Cov:32
GnomAD4 genome	AF: 0.213	AC:32430	Hom:5003	AN:152116	Cov:32
TOPMed (Bravo)	AF: 0.221	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.143	AC:102672	Hom:11063	AN:720022	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.187	AC:437	Hom:52	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.191	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.0700	AC:21	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.261	AC:904	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.184	AC:1331	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.364	AC:64	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.143	AC:17576	Hom:1265	AN:122722	Cov:
Turkish Variome	AF: 0.191	AC:295	Hom:32	AN:1546	Cov:
UK10K	AF: 0.0968	AC:732	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.186	AC:1671	Hom:168	AN:8960	Cov:

Showing 14 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	11
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.6
DANN	Benign	0.84
GPN-Star LLR	N/A	-1.8
GPN-Star score	N/A	1.8
Mutation Taster	N/A	99/1	polymorphism (auto)
PhyloP100	Benign	-2.7

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

Publications

Other links and lift over