dbSNP rs10411210: RHPN2:c.185+2855G>A (chr19-33041394-C-T) – ACMG Classification: Benign (-12 pts)

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.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

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

GnomAD3 genomes

AF:

0.213

AC:

32348

AN:

151998

Hom.:

4972

Cov.:

show subpopulations

Gnomad AFR

AF:

0.426

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.345

Gnomad FIN

AF:

0.146

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.180

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

GnomAD4 genome

AF:

0.213

AC:

32430

AN:

152116

Hom.:

5003

Cov.:

AF XY:

0.216

AC XY:

16071

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.426

AC:

17682

AN:

41470

American (AMR)

AF:

0.159

AC:

2428

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

670

AN:

3468

East Asian (EAS)

AF:

0.180

AC:

932

AN:

5174

South Asian (SAS)

AF:

0.344

AC:

1662

AN:

4826

European-Finnish (FIN)

AF:

0.146

AC:

1548

AN:

10582

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6955

AN:

68006

Other (OTH)

AF:

0.182

AC:

383

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1153

2307

3460

4614

5767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

332

664

996

1328

1660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.138

Hom.:

9354

Bravo

AF:

0.221

Asia WGS

AF:

0.261

AC:

904

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.143

AC:

17576

AN:

122722

Turkish Variome

AF:

0.191

AC:

295

AN:

1546

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.186

AC:

1671

AN:

8960

Hom.:

168

ABraOM SABE-WGS-1171

AF:

0.187

AC:

437

AN:

2342

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

3.6

(source)

DANN

Benign

0.84

PhyloP100

-2.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over