rs2465520

Variant names:

• chr2-203439491-G-A
• rs2465520
• NM_213589.3:c.3699C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-203439491-G-A
• chr2-203439491-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_213589.3(RAPH1):​c.3699C>T​(p.Pro1233Pro) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 14 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAPH1	NM_213589.3	c.3699C>T	p.Pro1233Pro	synonymous_variant	Exon 14 of 14	ENST00000319170.10	NP_998754.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAPH1	ENST00000319170.10	c.3699C>T	p.Pro1233Pro	synonymous_variant	Exon 14 of 14	1	NM_213589.3	ENSP00000316543.5

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23795 AN: 151984 Hom.: 2600 Cov.: 32

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

GnomAD2 exomes AF: 0.109 AC: 27285 AN: 251130 AF XY: 0.104

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 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.: 34 AF XY: 0.108 AC XY: 78233 AN XY: 727108

African (AFR) AF: 0.315 AC: 10555 AN: 33476

American (AMR) AF: 0.0878 AC: 3929 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 3163 AN: 26134

East Asian (EAS) AF: 0.0582 AC: 2312 AN: 39700

South Asian (SAS) AF: 0.0587 AC: 5065 AN: 86252

European-Finnish (FIN) AF: 0.0921 AC: 4905 AN: 53274

Middle Eastern (MID) AF: 0.0929 AC: 536 AN: 5768

European-Non Finnish (NFE) AF: 0.110 AC: 122747 AN: 1111914

Other (OTH) AF: 0.114 AC: 6856 AN: 60388

GnomAD4 genome AF: 0.157 AC: 23817 AN: 152102 Hom.: 2604 Cov.: 32 AF XY: 0.153 AC XY: 11349 AN XY: 74360

African (AFR) AF: 0.306 AC: 12683 AN: 41440

American (AMR) AF: 0.110 AC: 1681 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3472

East Asian (EAS) AF: 0.0785 AC: 407 AN: 5182

South Asian (SAS) AF: 0.0598 AC: 288 AN: 4818

European-Finnish (FIN) AF: 0.0955 AC: 1012 AN: 10594

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6992 AN: 67984

Other (OTH) AF: 0.141 AC: 296 AN: 2106

Alfa AF: 0.127 Hom.: 2801

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
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=98/2	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: rs2465520; hg19: chr2-204304214;