Variant 19-32996086-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033103.5(RHPN2):c.1360T>G(p.Tyr454Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0039 in 1,613,980 control chromosomes in the GnomAD database, including 193 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 106 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 87 hom. )

Consequence

RHPN2
NM_033103.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.61

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035038292).

BP6

Variant 19-32996086-A-C is Benign according to our data. Variant chr19-32996086-A-C is described in ClinVar as [Benign]. Clinvar id is 791356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHPN2	NM_033103.5 linkuse as main transcript	c.1360T>G	p.Tyr454Asp	missense_variant	11/15	ENST00000254260.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHPN2	ENST00000254260.8 linkuse as main transcript	c.1360T>G	p.Tyr454Asp	missense_variant	11/15	1	NM_033103.5	P1	Q8IUC4-1
RHPN2	ENST00000544458.6 linkuse as main transcript	n.1689T>G		non_coding_transcript_exon_variant	8/12	2
RHPN2	ENST00000585641.1 linkuse as main transcript	n.376T>G		non_coding_transcript_exon_variant	1/2	5
RHPN2	ENST00000588388.5 linkuse as main transcript	c.*897T>G		3_prime_UTR_variant, NMD_transcript_variant	10/14	2

Frequencies

GnomAD3 genomes

AF:

0.0203

AC:

3085

AN:

152182

Hom.:

106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0704

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00563

AC:

1414

AN:

251184

Hom.:

AF XY:

0.00417

AC XY:

566

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.0737

Gnomad AMR exome

AF:

0.00396

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000449

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00219

AC:

3200

AN:

1461680

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

1398

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.0726

Gnomad4 AMR exome

AF:

0.00400

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000214

Gnomad4 OTH exome

AF:

0.00512

GnomAD4 genome

AF:

0.0203

AC:

3092

AN:

152300

Hom.:

106

Cov.:

AF XY:

0.0197

AC XY:

1468

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0703

Gnomad4 AMR

AF:

0.00784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00512

Hom.:

Bravo

AF:

0.0228

ESP6500AA

AF:

0.0708

AC:

312

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00692

AC:

840

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.5

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-8.4

REVEL

Benign

0.18

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

0.98

Vest4

0.51

MVP

0.47

MPC

0.64

ClinPred

0.11

GERP RS

3.8

Varity_R

0.87

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over