12-68650387-A-AT

Position:

• chr12-68650387-A-AT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001010942.3(RAP1B):​c.58-4dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000363 in 1,369,916 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RAP1B NM_001010942.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.94

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 12-68650387-A-AT is Benign according to our data. Variant chr12-68650387-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 3041426.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 497 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAP1B	NM_001010942.3	c.58-4dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000250559.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAP1B	ENST00000250559.14	c.58-4dup		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001010942.3	P1

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151256 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000363 AC: 497 AN: 1369916 Hom.: 0 Cov.: 29 AF XY: 0.000370 AC XY: 252 AN XY: 681840

Gnomad4 AFR exome AF: 0.000545

Gnomad4 AMR exome AF: 0.00154

Gnomad4 ASJ exome AF: 0.000420

Gnomad4 EAS exome AF: 0.000533

Gnomad4 SAS exome AF: 0.00114

Gnomad4 FIN exome AF: 0.000388

Gnomad4 NFE exome AF: 0.000255

Gnomad4 OTH exome AF: 0.000481

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000198 AC: 3 AN: 151256 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 73838

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000295

Gnomad4 OTH AF: 0.00

Asia WGS AF: 0.00145 AC: 5 AN: 3460

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

RAP1B-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 06, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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: rs747450838; hg19: chr12-69044167;