rs7259371

chr19-33043735-G-Achr19-33043735-G-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+514C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,034 control chromosomes in the GnomAD database, including 15,366 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 0.39 (15366 hom., cov: 31)
• Consequence: RHPN2 NM_033103.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.611

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHPN2	NM_033103.5	c.185+514C>T		intron_variant		ENST00000254260.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHPN2	ENST00000254260.8	c.185+514C>T		intron_variant		1	NM_033103.5	P1
RHPN2	ENST00000588388.5	c.185+514C>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59119 AN: 151916 Hom.: 15322 Cov.: 31

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.390 AC: 59225 AN: 152034 Hom.: 15366 Cov.: 31 AF XY: 0.395 AC XY: 29366 AN XY: 74330

Gnomad4 AFR AF: 0.708

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.495

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.384

Alfa AF: 0.232 Hom.: 3647

Bravo AF: 0.423

Asia WGS AF: 0.527 AC: 1830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.12
Dann	Benign	0.53

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: rs7259371; hg19: chr19-33534641;