Variant chr12-68648715-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001010942.3(RAP1B):c.-10A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.006 in 1,611,240 control chromosomes in the GnomAD database, including 238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0099 ( 51 hom., cov: 31)

Exomes 𝑓: 0.0056 ( 187 hom. )

Consequence

RAP1B
NM_001010942.3 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.103

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 12-68648715-A-G is Benign according to our data. Variant chr12-68648715-A-G is described in ClinVar as [Benign]. Clinvar id is 1254710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAP1B	NM_001010942.3 linkuse as main transcript	c.-10A>G		5_prime_UTR_variant	2/8	ENST00000250559.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAP1B	ENST00000250559.14 linkuse as main transcript	c.-10A>G		5_prime_UTR_variant	2/8	1	NM_001010942.3	P1	P61224-1

Frequencies

GnomAD3 genomes

AF:

0.00994

AC:

1510

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000750

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0172

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0648

Gnomad SAS

AF:

0.00353

Gnomad FIN

AF:

0.0703

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00166

Gnomad OTH

AF:

0.00576

GnomAD3 exomes

AF:

0.0172

AC:

4273

AN:

248568

Hom.:

112

AF XY:

0.0156

AC XY:

2092

AN XY:

134478

show subpopulations

Gnomad AFR exome

AF:

0.000679

Gnomad AMR exome

AF:

0.0413

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0707

Gnomad SAS exome

AF:

0.00176

Gnomad FIN exome

AF:

0.0588

Gnomad NFE exome

AF:

0.00182

Gnomad OTH exome

AF:

0.0112

GnomAD4 exome

AF:

0.00559

AC:

8160

AN:

1459226

Hom.:

187

Cov.:

AF XY:

0.00538

AC XY:

3903

AN XY:

725990

show subpopulations

Gnomad4 AFR exome

AF:

0.000602

Gnomad4 AMR exome

AF:

0.0367

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0511

Gnomad4 SAS exome

AF:

0.00187

Gnomad4 FIN exome

AF:

0.0545

Gnomad4 NFE exome

AF:

0.000962

Gnomad4 OTH exome

AF:

0.00602

GnomAD4 genome

AF:

0.00995

AC:

1512

AN:

152014

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

1014

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.000747

Gnomad4 AMR

AF:

0.0172

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0651

Gnomad4 SAS

AF:

0.00374

Gnomad4 FIN

AF:

0.0703

Gnomad4 NFE

AF:

0.00166

Gnomad4 OTH

AF:

0.00570

Alfa

AF:

0.00271

Hom.:

Bravo

AF:

0.00732

Asia WGS

AF:

0.0220

AC:

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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