rs2246118

Variant names:

• chr2-203462916-T-C
• rs2246118
• NM_213589.3:c.733-991A>G

Variant summary

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

The NM_213589.3(RAPH1):​c.733-991A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 151,960 control chromosomes in the GnomAD database, including 29,123 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 0.61 (29123 hom., cov: 32)
• Consequence: RAPH1 NM_213589.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• Publications: 7 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213589.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPH1	NM_213589.3	MANE Select	c.733-991A>G		intron	N/A	NP_998754.1	Q70E73-10
	RAPH1	NM_001439019.1		c.889-991A>G		intron	N/A	NP_001425948.1
	RAPH1	NM_001439027.1		c.814-991A>G		intron	N/A	NP_001425956.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAPH1	ENST00000319170.10	TSL:1 MANE Select	c.733-991A>G		intron	N/A	ENSP00000316543.5	Q70E73-10
	RAPH1	ENST00000453034.5	TSL:1	c.889-991A>G		intron	N/A	ENSP00000406662.1	Q70E73-6
	RAPH1	ENST00000308091.8	TSL:1	c.889-991A>G		intron	N/A	ENSP00000311293.4	Q70E73-9

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93068 AN: 151842 Hom.: 29104 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.613 AC: 93121 AN: 151960 Hom.: 29123 Cov.: 32 AF XY: 0.609 AC XY: 45203 AN XY: 74270

African (AFR) AF: 0.701 AC: 29066 AN: 41450

American (AMR) AF: 0.577 AC: 8808 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2392 AN: 3466

East Asian (EAS) AF: 0.378 AC: 1952 AN: 5160

South Asian (SAS) AF: 0.662 AC: 3180 AN: 4806

European-Finnish (FIN) AF: 0.476 AC: 5011 AN: 10518

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40581 AN: 67968

Other (OTH) AF: 0.620 AC: 1309 AN: 2112

Alfa AF: 0.594 Hom.: 3397

Bravo AF: 0.620

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.67
PhyloP100		-0.14
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2246118;

hg19: chr2-204327639;