NM_033103.5:c.185+514C>T

Variant names:

• chr19-33043735-G-A
• rs7259371
• NM_033103.5:c.185+514C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033103.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHPN2	NM_033103.5	MANE Select	c.185+514C>T		intron	N/A	NP_149094.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHPN2	ENST00000254260.8	TSL:1 MANE Select	c.185+514C>T		intron	N/A	ENSP00000254260.2
	RHPN2	ENST00000588388.5	TSL:2	n.185+514C>T		intron	N/A	ENSP00000465898.1

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

African (AFR) AF: 0.708 AC: 29333 AN: 41458

American (AMR) AF: 0.459 AC: 7002 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1347 AN: 3470

East Asian (EAS) AF: 0.491 AC: 2539 AN: 5170

South Asian (SAS) AF: 0.495 AC: 2383 AN: 4812

European-Finnish (FIN) AF: 0.220 AC: 2324 AN: 10568

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13178 AN: 67982

Other (OTH) AF: 0.384 AC: 811 AN: 2114

Alfa AF: 0.227 Hom.: 4792

Bravo AF: 0.423

Asia WGS AF: 0.527 AC: 1830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.53
PhyloP100		-0.61
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: rs7259371; hg19: chr19-33534641;