12-68653883-G-A

Position:

• chr12-68653883-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001010942.3(RAP1B):​c.184-229G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 151,422 control chromosomes in the GnomAD database, including 4,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.24 (4734 hom., cov: 30)
• Consequence: RAP1B NM_001010942.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.43

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 12-68653883-G-A is Benign according to our data. Variant chr12-68653883-G-A is described in ClinVar as [Benign]. Clinvar id is 1246821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAP1B	NM_001010942.3	c.184-229G>A		intron_variant		ENST00000250559.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAP1B	ENST00000250559.14	c.184-229G>A		intron_variant		1	NM_001010942.3	P1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 36966 AN: 151304 Hom.: 4735 Cov.: 30

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.229

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.244 AC: 36990 AN: 151422 Hom.: 4734 Cov.: 30 AF XY: 0.248 AC XY: 18338 AN XY: 73950

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.228

Alfa AF: 0.225 Hom.: 486

Bravo AF: 0.245

Asia WGS AF: 0.345 AC: 1203 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.74
DANN	Benign	0.60

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: rs7974454; hg19: chr12-69047663;