Variant 2-203440370-T-C 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.2820A>G(p.Pro940Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 1,578,334 control chromosomes in the GnomAD database, including 236,589 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 0.47 ( 17036 hom., cov: 25)

Exomes 𝑓: 0.55 ( 219553 hom. )

Consequence

RAPH1
NM_213589.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.59

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=-0.94).

BP7

Synonymous conserved (PhyloP=-3.59 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.611 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.2820A>G	p.Pro940Pro	synonymous_variant	14/14	ENST00000319170.10	NP_998754.1	Q70E73-10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAPH1	ENST00000319170.10 linkuse as main transcript	c.2820A>G	p.Pro940Pro	synonymous_variant	14/14	1	NM_213589.3	ENSP00000316543.5		Q70E73-10

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

67371

AN:

143570

Hom.:

17052

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.652

Gnomad AMR

AF:

0.507

Gnomad ASJ

AF:

0.678

Gnomad EAS

AF:

0.371

Gnomad SAS

AF:

0.631

Gnomad FIN

AF:

0.473

Gnomad MID

AF:

0.718

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.520

GnomAD3 exomes

AF:

0.514

AC:

124415

AN:

242010

Hom.:

33639

AF XY:

0.530

AC XY:

69250

AN XY:

130742

show subpopulations

Gnomad AFR exome

AF:

0.208

Gnomad AMR exome

AF:

0.454

Gnomad ASJ exome

AF:

0.672

Gnomad EAS exome

AF:

0.366

Gnomad SAS exome

AF:

0.628

Gnomad FIN exome

AF:

0.453

Gnomad NFE exome

AF:

0.566

Gnomad OTH exome

AF:

0.565

GnomAD4 exome

AF:

0.549

AC:

787968

AN:

1434678

Hom.:

219553

Cov.:

AF XY:

0.553

AC XY:

393572

AN XY:

711584

show subpopulations

Gnomad4 AFR exome

AF:

0.210

Gnomad4 AMR exome

AF:

0.456

Gnomad4 ASJ exome

AF:

0.674

Gnomad4 EAS exome

AF:

0.320

Gnomad4 SAS exome

AF:

0.630

Gnomad4 FIN exome

AF:

0.475

Gnomad4 NFE exome

AF:

0.565

Gnomad4 OTH exome

AF:

0.553

GnomAD4 genome

AF:

0.469

AC:

67351

AN:

143656

Hom.:

17036

Cov.:

AF XY:

0.469

AC XY:

32748

AN XY:

69834

show subpopulations

Gnomad4 AFR

AF:

0.239

Gnomad4 AMR

AF:

0.506

Gnomad4 ASJ

AF:

0.678

Gnomad4 EAS

AF:

0.371

Gnomad4 SAS

AF:

0.630

Gnomad4 FIN

AF:

0.473

Gnomad4 NFE

AF:

0.569

Gnomad4 OTH

AF:

0.515

Alfa

AF:

0.449

Hom.:

3033

Bravo

AF:

0.439

Asia WGS

AF:

0.476

AC:

1657

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

1.3

DANN

Benign

0.56

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