rs10424333

Positions:

• chr19-33036690-C-G
• chr19-33036690-C-T

Variant summary

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

The NM_033103.5(RHPN2):​c.185+7559G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,182 control chromosomes in the GnomAD database, including 1,951 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 0.15 (1951 hom., cov: 32)
• Consequence: RHPN2 NM_033103.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHPN2	NM_033103.5	c.185+7559G>C		intron_variant		ENST00000254260.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHPN2	ENST00000254260.8	c.185+7559G>C		intron_variant		1	NM_033103.5	P1
RHPN2	ENST00000588388.5	c.185+7559G>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22570 AN: 152064 Hom.: 1952 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.0991

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.148 AC: 22595 AN: 152182 Hom.: 1951 Cov.: 32 AF XY: 0.154 AC XY: 11420 AN XY: 74384

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.0991

Gnomad4 OTH AF: 0.129

Alfa AF: 0.0568 Hom.: 64

Bravo AF: 0.149

Asia WGS AF: 0.246 AC: 853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.23

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: rs10424333; hg19: chr19-33527596;