rs2287921

Positions:

• chr19-48725015-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017805.3(RASIP1):​c.2128-55A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,582,496 control chromosomes in the GnomAD database, including 187,230 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 0.37 (12551 hom., cov: 33)
  • Exomes 𝑓: 0.48 (174679 hom.)
• Consequence: RASIP1 NM_017805.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139

Genes affected

RASIP1 (HGNC:24716): (Ras interacting protein 1) Enables GTPase binding activity and protein homodimerization activity. Involved in several processes, including negative regulation of Rho protein signal transduction; negative regulation of Rho-dependent protein serine/threonine kinase activity; and positive regulation of integrin activation. Located in cell-cell junction. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

RASIP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RASIP1	NM_017805.3	c.2128-55A>G		intron_variant		ENST00000222145.9	NP_060275.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RASIP1	ENST00000222145.9	c.2128-55A>G		intron_variant		1	NM_017805.3	ENSP00000222145.3
RASIP1	ENST00000599291.1	c.415-55A>G		intron_variant		3		ENSP00000471633.1
RASIP1	ENST00000601530.1	n.567A>G		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56576 AN: 151996 Hom.: 12563 Cov.: 33

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.0218

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.412

GnomAD4 exome AF: 0.478 AC: 683264 AN: 1430380 Hom.: 174679 Cov.: 32 AF XY: 0.473 AC XY: 334654 AN XY: 707816

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.481

Gnomad4 EAS exome AF: 0.0361

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.430

Gnomad4 NFE exome AF: 0.529

Gnomad4 OTH exome AF: 0.460

GnomAD4 genome AF: 0.372 AC: 56553 AN: 152116 Hom.: 12551 Cov.: 33 AF XY: 0.363 AC XY: 27019 AN XY: 74360

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.0218

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.406

Alfa AF: 0.484 Hom.: 28760

Bravo AF: 0.359

Asia WGS AF: 0.119 AC: 421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.75

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: rs2287921; hg19: chr19-49228272; COSMIC: COSV55804058; COSMIC: COSV55804058;