NM_033103.5:c.186-7381A>C

Variant names:

• chr19-33034013-T-G
• rs73039434
• NM_033103.5:c.186-7381A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033103.5(RHPN2):​c.186-7381A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 151,586 control chromosomes in the GnomAD database, including 1,771 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 0.13 (1771 hom., cov: 30)
• Consequence: RHPN2 NM_033103.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHPN2	NM_033103.5	c.186-7381A>C		intron_variant	Intron 2 of 14	ENST00000254260.8	NP_149094.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RHPN2	ENST00000254260.8	c.186-7381A>C		intron_variant	Intron 2 of 14	1	NM_033103.5	ENSP00000254260.2
RHPN2	ENST00000588388.5	n.186-7381A>C		intron_variant	Intron 2 of 13	2		ENSP00000465898.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19338 AN: 151470 Hom.: 1766 Cov.: 30

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.0644

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0586

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.128 AC: 19354 AN: 151586 Hom.: 1771 Cov.: 30 AF XY: 0.130 AC XY: 9651 AN XY: 74078

African (AFR) AF: 0.243 AC: 10021 AN: 41246

American (AMR) AF: 0.102 AC: 1554 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3470

East Asian (EAS) AF: 0.192 AC: 981 AN: 5116

South Asian (SAS) AF: 0.244 AC: 1168 AN: 4780

European-Finnish (FIN) AF: 0.0644 AC: 676 AN: 10492

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.0586 AC: 3980 AN: 67930

Other (OTH) AF: 0.110 AC: 232 AN: 2108

Alfa AF: 0.0862 Hom.: 1592

Bravo AF: 0.134

Asia WGS AF: 0.203 AC: 705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.24
DANN	Benign	0.60
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73039434; hg19: chr19-33524919;