12-68650696-T-G

Position:

• chr12-68650696-T-G

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.126+228T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0309 in 285,756 control chromosomes in the GnomAD database, including 738 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.052 (675 hom., cov: 32)
  • Exomes 𝑓: 0.0068 (63 hom.)
• Consequence: RAP1B NM_001010942.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.783

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=-0.86).
• BP6: Variant 12-68650696-T-G is Benign according to our data. Variant chr12-68650696-T-G is described in ClinVar as [Benign]. Clinvar id is 1266904.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAP1B	NM_001010942.3	c.126+228T>G		intron_variant		ENST00000250559.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAP1B	ENST00000250559.14	c.126+228T>G		intron_variant		1	NM_001010942.3	P1

Frequencies

GnomAD3 genomes AF: 0.0521 AC: 7926 AN: 152098 Hom.: 676 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0203

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.0268

GnomAD4 exome AF: 0.00676 AC: 903 AN: 133540 Hom.: 63 Cov.: 4 AF XY: 0.00581 AC XY: 395 AN XY: 67934

Gnomad4 AFR exome AF: 0.186

Gnomad4 AMR exome AF: 0.0203

Gnomad4 ASJ exome AF: 0.000466

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000144

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000409

Gnomad4 OTH exome AF: 0.0154

GnomAD4 genome AF: 0.0522 AC: 7939 AN: 152216 Hom.: 675 Cov.: 32 AF XY: 0.0512 AC XY: 3812 AN XY: 74438

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.0203

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000617

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0413 Hom.: 61

Bravo AF: 0.0606

Asia WGS AF: 0.00953 AC: 34 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

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.9
DANN	Benign	0.61

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: rs7304966; hg19: chr12-69044476;