19-33041394-C-T

Position:

• chr19-33041394-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+2855G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,116 control chromosomes in the GnomAD database, including 5,003 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 0.21 (5003 hom., cov: 32)
• Consequence: RHPN2 NM_033103.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73

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=-0.56).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHPN2	NM_033103.5	c.185+2855G>A		intron_variant		ENST00000254260.8	NP_149094.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHPN2	ENST00000254260.8	c.185+2855G>A		intron_variant		1	NM_033103.5	ENSP00000254260	P1
RHPN2	ENST00000588388.5	c.185+2855G>A		intron_variant, NMD_transcript_variant		2		ENSP00000465898

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32348 AN: 151998 Hom.: 4972 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.213 AC: 32430 AN: 152116 Hom.: 5003 Cov.: 32 AF XY: 0.216 AC XY: 16071 AN XY: 74368

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.344

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.182

Alfa AF: 0.128 Hom.: 3223

Bravo AF: 0.221

Asia WGS AF: 0.261 AC: 904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.6
DANN	Benign	0.84

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: rs10411210; hg19: chr19-33532300; COSMIC: COSV54274329;