Genetic Variant RAP1B:c.57+129T>G (chr12-68648910-T-G) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001010942.3(RAP1B):c.57+129T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 827,046 control chromosomes in the GnomAD database, including 34,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4768 hom., cov: 31)

Exomes 𝑓: 0.29 ( 30038 hom. )

Consequence

RAP1B
NM_001010942.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.40

Variant links:

Genes affected

RAP1B (HGNC:9857): (RAP1B, member of RAS oncogene family) This gene encodes a member of the RAS-like small GTP-binding protein superfamily. Members of this family regulate multiple cellular processes including cell adhesion and growth and differentiation. This protein localizes to cellular membranes and has been shown to regulate integrin-mediated cell signaling. This protein also plays a role in regulating outside-in signaling in platelets. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 3, 5, 6 and 9. [provided by RefSeq, Oct 2011]

RAP1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 12-68648910-T-G is Benign according to our data. Variant chr12-68648910-T-G is described in ClinVar as [Benign]. Clinvar id is 1283372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAP1B	NM_001010942.3 link	c.57+129T>G		intron_variant	Intron 2 of 7	ENST00000250559.14	NP_001010942.1	P61224-1A0A024RB87

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAP1B	ENST00000250559.14 link	c.57+129T>G		intron_variant	Intron 2 of 7	1	NM_001010942.3	ENSP00000250559.9		P61224-1

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34713

AN:

151990

Hom.:

4774

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0886

Gnomad AMI

AF:

0.345

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.121

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.223

GnomAD4 exome

AF:

0.288

AC:

194078

AN:

674938

Hom.:

30038

Cov.:

AF XY:

0.282

AC XY:

96748

AN XY:

343512

show subpopulations

Gnomad4 AFR exome

AF:

0.0846

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.202

Gnomad4 EAS exome

AF:

0.133

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.341

Gnomad4 NFE exome

AF:

0.323

Gnomad4 OTH exome

AF:

0.261

GnomAD4 genome

AF:

0.228

AC:

34706

AN:

152108

Hom.:

4768

Cov.:

AF XY:

0.224

AC XY:

16691

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0884

Gnomad4 AMR

AF:

0.190

Gnomad4 ASJ

AF:

0.215

Gnomad4 EAS

AF:

0.122

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.342

Gnomad4 NFE

AF:

0.320

Gnomad4 OTH

AF:

0.220

Alfa

AF:

0.281

Hom.:

2533

Bravo

AF:

0.211

Asia WGS

AF:

0.124

AC:

431

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over