chr12-68650501-G-T

Position:

• chr12-68650501-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001010942.3(RAP1B):​c.126+33G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00975 in 1,396,192 control chromosomes in the GnomAD database, including 1,109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.051 (650 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (459 hom.)
• Consequence: RAP1B NM_001010942.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.364

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 12-68650501-G-T is Benign according to our data. Variant chr12-68650501-G-T is described in ClinVar as [Benign]. Clinvar id is 1267109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAP1B	NM_001010942.3	c.126+33G>T		intron_variant		ENST00000250559.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAP1B	ENST00000250559.14	c.126+33G>T		intron_variant		1	NM_001010942.3	P1

Frequencies

GnomAD3 genomes AF: 0.0513 AC: 7788 AN: 151850 Hom.: 651 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000618

Gnomad OTH AF: 0.0264

GnomAD3 exomes AF: 0.0121 AC: 1859 AN: 153666 Hom.: 138 AF XY: 0.00842 AC XY: 723 AN XY: 85882

Gnomad AFR exome AF: 0.171

Gnomad AMR exome AF: 0.00947

Gnomad ASJ exome AF: 0.000668

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000444

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000413

Gnomad OTH exome AF: 0.00757

GnomAD4 exome AF: 0.00467 AC: 5812 AN: 1244224 Hom.: 459 Cov.: 22 AF XY: 0.00412 AC XY: 2552 AN XY: 619708

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.0121

Gnomad4 ASJ exome AF: 0.000433

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000424

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000328

Gnomad4 OTH exome AF: 0.0115

GnomAD4 genome AF: 0.0513 AC: 7800 AN: 151968 Hom.: 650 Cov.: 32 AF XY: 0.0503 AC XY: 3738 AN XY: 74282

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.0199

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000618

Gnomad4 OTH AF: 0.0262

Alfa AF: 0.0272 Hom.: 66

Bravo AF: 0.0595

Asia WGS AF: 0.00925 AC: 33 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 22, 2021	- -
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	-0.70
CADD	Benign	6.3
DANN	Benign	0.76

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: rs12310406; hg19: chr12-69044281;