rs2246118

chr2-203462916-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAPH1	NM_213589.3	c.733-991A>G		intron_variant		ENST00000319170.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAPH1	ENST00000319170.10	c.733-991A>G		intron_variant		1	NM_213589.3

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

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.620

Alfa AF: 0.594 Hom.: 3397

Bravo AF: 0.620

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	2.1
Dann	Benign	0.67

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

Other links and lift over

dbSNP: rs2246118; hg19: chr2-204327639;