Menu
GeneBe

1-111697503-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_002884.4(RAP1A):c.183+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 1,611,104 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 25 hom., cov: 31)
Exomes 𝑓: 0.0011 ( 36 hom. )

Consequence

RAP1A
NM_002884.4 splice_donor_region, intron

Scores

2
Splicing: ADA: 0.0002169
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.241
Variant links:
Genes affected
RAP1A (HGNC:9855): (RAP1A, member of RAS oncogene family) This gene encodes a member of the Ras family of small GTPases. The encoded protein undergoes a change in conformational state and activity, depending on whether it is bound to GTP or GDP. This protein is activated by several types of guanine nucleotide exchange factors (GEFs), and inactivated by two groups of GTPase-activating proteins (GAPs). The activation status of the encoded protein is therefore affected by the balance of intracellular levels of GEFs and GAPs. The encoded protein regulates signaling pathways that affect cell proliferation and adhesion, and may play a role in tumor malignancy. Pseudogenes of this gene have been defined on chromosomes 14 and 17. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
INKA2 (HGNC:28045): (inka box actin regulator 2) Enables protein kinase binding activity. Predicted to be involved in negative regulation of catalytic activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-111697503-G-A is Benign according to our data. Variant chr1-111697503-G-A is described in ClinVar as [Benign]. Clinvar id is 718795.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0108 (1647/152100) while in subpopulation AFR AF= 0.0383 (1591/41498). AF 95% confidence interval is 0.0368. There are 25 homozygotes in gnomad4. There are 776 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1644 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RAP1ANM_002884.4 linkuse as main transcriptc.183+6G>A splice_donor_region_variant, intron_variant ENST00000369709.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RAP1AENST00000369709.4 linkuse as main transcriptc.183+6G>A splice_donor_region_variant, intron_variant 1 NM_002884.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0108
AC:
1644
AN:
151982
Hom.:
25
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0384
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00223
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00625
GnomAD3 exomes
AF:
0.00271
AC:
678
AN:
249994
Hom.:
11
AF XY:
0.00181
AC XY:
245
AN XY:
135138
show subpopulations
Gnomad AFR exome
AF:
0.0388
Gnomad AMR exome
AF:
0.00123
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000658
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000353
Gnomad OTH exome
AF:
0.000329
GnomAD4 exome
AF:
0.00112
AC:
1640
AN:
1459004
Hom.:
36
Cov.:
33
AF XY:
0.000955
AC XY:
693
AN XY:
725866
show subpopulations
Gnomad4 AFR exome
AF:
0.0414
Gnomad4 AMR exome
AF:
0.00140
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000583
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000477
Gnomad4 OTH exome
AF:
0.00226
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0108
AC:
1647
AN:
152100
Hom.:
25
Cov.:
31
AF XY:
0.0104
AC XY:
776
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.0383
Gnomad4 AMR
AF:
0.00223
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00618
Alfa
AF:
0.00615
Hom.:
6
Bravo
AF:
0.0126
Asia WGS
AF:
0.00260
AC:
10
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
Cadd
Benign
12
Dann
Benign
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00022
dbscSNV1_RF
Benign
0.042
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.

Other links and lift over

dbSNP: rs72991083; hg19: chr1-112240125; API