rs73039434

Positions:

• chr19-33034013-T-G

Variant summary

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

The NM_033103.5(RHPN2):​c.186-7381A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 151,586 control chromosomes in the GnomAD database, including 1,771 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 0.13 (1771 hom., cov: 30)
• Consequence: RHPN2 NM_033103.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHPN2	NM_033103.5	c.186-7381A>C		intron_variant		ENST00000254260.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHPN2	ENST00000254260.8	c.186-7381A>C		intron_variant		1	NM_033103.5	P1
RHPN2	ENST00000588388.5	c.186-7381A>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19338 AN: 151470 Hom.: 1766 Cov.: 30

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.0644

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0586

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.128 AC: 19354 AN: 151586 Hom.: 1771 Cov.: 30 AF XY: 0.130 AC XY: 9651 AN XY: 74078

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.0644

Gnomad4 NFE AF: 0.0586

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0829 Hom.: 279

Bravo AF: 0.134

Asia WGS AF: 0.203 AC: 705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.24
DANN	Benign	0.60

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: rs73039434; hg19: chr19-33524919;