Genetic Variant RASIP1:c.2128-55A>G (chr19-48725015-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.139

Publications

74 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017805.3. 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
	RASIP1	NM_017805.3	MANE Select	c.2128-55A>G		intron	N/A	NP_060275.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RASIP1	ENST00000222145.9	TSL:1 MANE Select	c.2128-55A>G	intron	N/A	ENSP00000222145.3	Q5U651
RASIP1	ENST00000963671.1		c.2128-55A>G	intron	N/A	ENSP00000633730.1
RASIP1	ENST00000862294.1		c.2128-55A>G	intron	N/A	ENSP00000532353.1

Frequencies

GnomAD3 genomes

AF:

0.372

AC:

56576

AN:

151996

Hom.:

12563

Cov.:

show subpopulations

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.:

AF XY:

0.473

AC XY:

334654

AN XY:

707816

show subpopulations

African (AFR)

AF:

0.165

AC:

5402

AN:

32826

American (AMR)

AF:

0.266

AC:

11388

AN:

42760

Ashkenazi Jewish (ASJ)

AF:

0.481

AC:

11743

AN:

24402

East Asian (EAS)

AF:

0.0361

AC:

1417

AN:

39244

South Asian (SAS)

AF:

0.289

AC:

23943

AN:

82772

European-Finnish (FIN)

AF:

0.430

AC:

22365

AN:

52068

Middle Eastern (MID)

AF:

0.501

AC:

2822

AN:

5634

European-Non Finnish (NFE)

AF:

0.529

AC:

577027

AN:

1091696

Other (OTH)

AF:

0.460

AC:

27157

AN:

58978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

18204

36408

54612

72816

91020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16318

32636

48954

65272

81590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.372

AC:

56553

AN:

152116

Hom.:

12551

Cov.:

AF XY:

0.363

AC XY:

27019

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.183

AC:

7602

AN:

41516

American (AMR)

AF:

0.352

AC:

5382

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.486

AC:

1685

AN:

3470

East Asian (EAS)

AF:

0.0218

AC:

113

AN:

5178

South Asian (SAS)

AF:

0.258

AC:

1243

AN:

4816

European-Finnish (FIN)

AF:

0.421

AC:

4454

AN:

10572

Middle Eastern (MID)

AF:

0.588

AC:

173

AN:

294

European-Non Finnish (NFE)

AF:

0.510

AC:

34676

AN:

67962

Other (OTH)

AF:

0.406

AC:

858

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1706

3412

5117

6823

8529

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.456

Hom.:

61826

Bravo

AF:

0.359

Asia WGS

AF:

0.119

AC:

421

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.2

(source)

DANN

Benign

0.75

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over