19-33026609-C-T

Variant names:

• chr19-33026609-C-T
• rs28626308
• NM_033103.5:c.209G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033103.5(RHPN2):​c.209G>A​(p.Arg70Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0674 in 1,607,944 control chromosomes in the GnomAD database, including 5,933 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 0.072 (529 hom., cov: 31)
  • Exomes 𝑓: 0.067 (5404 hom.)
• Consequence: RHPN2 NM_033103.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17
• Publications: 27 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019293427).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHPN2	NM_033103.5	MANE Select	c.209G>A	p.Arg70Gln	missense	Exon 3 of 15	NP_149094.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHPN2	ENST00000254260.8	TSL:1 MANE Select	c.209G>A	p.Arg70Gln	missense	Exon 3 of 15	ENSP00000254260.2	Q8IUC4-1
	RHPN2	ENST00000859930.1		c.186-4963G>A		intron	N/A	ENSP00000529989.1
	RHPN2	ENST00000544458.6	TSL:2	n.663G>A		non_coding_transcript_exon	Exon 1 of 12

Frequencies

GnomAD3 genomes AF: 0.0725 AC: 11011 AN: 151958 Hom.: 528 Cov.: 31

Gnomad AFR AF: 0.0680

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0859

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.0682

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0533

Gnomad OTH AF: 0.0679

GnomAD2 exomes AF: 0.0982 AC: 24323 AN: 247728 AF XY: 0.104

Gnomad AFR exome AF: 0.0683

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.157

Gnomad FIN exome AF: 0.0689

Gnomad NFE exome AF: 0.0537

Gnomad OTH exome AF: 0.0885

GnomAD4 exome AF: 0.0669 AC: 97387 AN: 1455868 Hom.: 5404 Cov.: 32 AF XY: 0.0728 AC XY: 52721 AN XY: 724462

African (AFR) AF: 0.0703 AC: 2353 AN: 33452

American (AMR) AF: 0.101 AC: 4520 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 3228 AN: 26094

East Asian (EAS) AF: 0.103 AC: 4092 AN: 39652

South Asian (SAS) AF: 0.245 AC: 21148 AN: 86220

European-Finnish (FIN) AF: 0.0709 AC: 3428 AN: 48328

Middle Eastern (MID) AF: 0.151 AC: 868 AN: 5762

European-Non Finnish (NFE) AF: 0.0476 AC: 52861 AN: 1111378

Other (OTH) AF: 0.0811 AC: 4889 AN: 60292

GnomAD4 genome AF: 0.0724 AC: 11011 AN: 152076 Hom.: 529 Cov.: 31 AF XY: 0.0768 AC XY: 5709 AN XY: 74320

African (AFR) AF: 0.0678 AC: 2815 AN: 41490

American (AMR) AF: 0.0856 AC: 1304 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3472

East Asian (EAS) AF: 0.142 AC: 731 AN: 5142

South Asian (SAS) AF: 0.230 AC: 1108 AN: 4820

European-Finnish (FIN) AF: 0.0682 AC: 723 AN: 10594

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0533 AC: 3622 AN: 68004

Other (OTH) AF: 0.0701 AC: 148 AN: 2112

Alfa AF: 0.0728 Hom.: 222

Bravo AF: 0.0720

TwinsUK AF: 0.0450 AC: 167

ALSPAC AF: 0.0506 AC: 195

ESP6500AA AF: 0.0651 AC: 287

ESP6500EA AF: 0.0543 AC: 467

ExAC AF: 0.0969 AC: 11762

Asia WGS AF: 0.177 AC: 615 AN: 3478

EpiCase AF: 0.0618

EpiControl AF: 0.0631

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.062
FATHMM_MKL	Benign	0.69	D
LIST_S2	Pathogenic	0.99	D
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.2
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.087
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.011	D
Polyphen		0.99	D
Vest4		0.22
MPC		1.0
ClinPred		0.022	T
GERP RS		2.8
Varity_R		0.23
gMVP		0.44
Mutation Taster		=95/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28626308; hg19: chr19-33517515; COSMIC: COSV54274321;