rs17841839

chr19-33026295-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.314+209G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0875 in 151,846 control chromosomes in the GnomAD database, including 719 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 0.088 (719 hom., cov: 30)
• Consequence: RHPN2 NM_033103.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHPN2	NM_033103.5	c.314+209G>A		intron_variant		ENST00000254260.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHPN2	ENST00000254260.8	c.314+209G>A		intron_variant		1	NM_033103.5	P1
RHPN2	ENST00000588388.5	c.314+209G>A		intron_variant, NMD_transcript_variant		2
RHPN2	ENST00000544458.6	n.768+209G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0875 AC: 13282 AN: 151728 Hom.: 719 Cov.: 30

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0976

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.0687

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0543

Gnomad OTH AF: 0.0857

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

GnomAD4 genome AF: 0.0875 AC: 13293 AN: 151846 Hom.: 719 Cov.: 30 AF XY: 0.0919 AC XY: 6817 AN XY: 74216

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0972

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.0687

Gnomad4 NFE AF: 0.0543

Gnomad4 OTH AF: 0.0886

Alfa AF: 0.0713 Hom.: 60

Bravo AF: 0.0892

Asia WGS AF: 0.180 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.3
Dann	Benign	0.79

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: rs17841839; hg19: chr19-33517201;