chr19-33030244-A-G

Position:

• chr19-33030244-A-G

Variant summary

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

The NM_033103.5(RHPN2):​c.186-3612T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,192 control chromosomes in the GnomAD database, including 1,025 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 0.10 (1025 hom., cov: 32)
• Consequence: RHPN2 NM_033103.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHPN2	NM_033103.5	c.186-3612T>C		intron_variant		ENST00000254260.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHPN2	ENST00000254260.8	c.186-3612T>C		intron_variant		1	NM_033103.5	P1
RHPN2	ENST00000588388.5	c.186-3612T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15661 AN: 152074 Hom.: 1022 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.0791

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0582

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.103 AC: 15686 AN: 152192 Hom.: 1025 Cov.: 32 AF XY: 0.107 AC XY: 7947 AN XY: 74398

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.0720

Gnomad4 NFE AF: 0.0582

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0790 Hom.: 173

Bravo AF: 0.106

Asia WGS AF: 0.185 AC: 644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.1
DANN	Benign	0.85

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: rs73039428; hg19: chr19-33521150;