Variant rs2465520 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_213589.3(RAPH1):c.3699C>T(p.Pro1233=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,732 control chromosomes in the GnomAD database, including 12,513 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 0.16 ( 2604 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9909 hom. )

Consequence

RAPH1
NM_213589.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.96

Variant links:

Genes affected

RAPH1 (HGNC:14436): (Ras association (RalGDS/AF-6) and pleckstrin homology domains 1) This gene encodes a protein that belongs to the Mig10/Rap1-interacting adaptor molecule/Lamellipodin family of adapter proteins, which function in cell migration. Members of this family contain pleckstrin-homology domains, Ras-association domains, and proline-rich C-termini. The protein encoded by this gene regulates actin dynamics through interaction with Ena/Vasodilator proteins as well as direct binding to filamentous actin to regulate actin network assembly. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

RAPH1 links:

ABI2 (HGNC:24011): (abl interactor 2) Enables several functions, including SH3 domain binding activity; identical protein binding activity; and ubiquitin protein ligase binding activity. Contributes to small GTPase binding activity. Involved in Rac protein signal transduction; positive regulation of cellular component organization; and zonula adherens assembly. Acts upstream of or within peptidyl-tyrosine phosphorylation. Located in several cellular components, including filopodium tip; lamellipodium; and nucleoplasm. Part of SCAR complex. Is active in adherens junction. Colocalizes with actin filament. [provided by Alliance of Genome Resources, Apr 2022]

ABI2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP7

Synonymous conserved (PhyloP=-1.96 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAPH1	NM_213589.3 linkuse as main transcript	c.3699C>T	p.Pro1233=	synonymous_variant	14/14	ENST00000319170.10	NP_998754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPH1	ENST00000319170.10 linkuse as main transcript	c.3699C>T	p.Pro1233=	synonymous_variant	14/14	1	NM_213589.3	ENSP00000316543		Q70E73-10

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23795

AN:

151984

Hom.:

2600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.306

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.110

Gnomad ASJ

AF:

0.119

Gnomad EAS

AF:

0.0791

Gnomad SAS

AF:

0.0597

Gnomad FIN

AF:

0.0955

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.142

GnomAD3 exomes

AF:

0.109

AC:

27285

AN:

251130

Hom.:

1943

AF XY:

0.104

AC XY:

14080

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.312

Gnomad AMR exome

AF:

0.0851

Gnomad ASJ exome

AF:

0.124

Gnomad EAS exome

AF:

0.0773

Gnomad SAS exome

AF:

0.0597

Gnomad FIN exome

AF:

0.0924

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.110

AC:

160068

AN:

1461630

Hom.:

9909

Cov.:

AF XY:

0.108

AC XY:

78233

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.315

Gnomad4 AMR exome

AF:

0.0878

Gnomad4 ASJ exome

AF:

0.121

Gnomad4 EAS exome

AF:

0.0582

Gnomad4 SAS exome

AF:

0.0587

Gnomad4 FIN exome

AF:

0.0921

Gnomad4 NFE exome

AF:

0.110

Gnomad4 OTH exome

AF:

0.114

GnomAD4 genome

AF:

0.157

AC:

23817

AN:

152102

Hom.:

2604

Cov.:

AF XY:

0.153

AC XY:

11349

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.306

Gnomad4 AMR

AF:

0.110

Gnomad4 ASJ

AF:

0.119

Gnomad4 EAS

AF:

0.0785

Gnomad4 SAS

AF:

0.0598

Gnomad4 FIN

AF:

0.0955

Gnomad4 NFE

AF:

0.103

Gnomad4 OTH

AF:

0.141

Alfa

AF:

0.135

Hom.:

841

Bravo

AF:

0.166

Asia WGS

AF:

0.0870

AC:

304

AN:

3478

EpiCase

AF:

0.0982

EpiControl

AF:

0.106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.8

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over