rs11177325

chr12-68671198-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010942.3(RAP1B):c.*11949C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 151,798 control chromosomes in the GnomAD database, including 4,600 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4599 hom., cov: 31)
  • Exomes 𝑓: 0.25 (1 hom.)
• Consequence: RAP1B NM_001010942.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAP1B	NM_001010942.3	c.*11949C>T		3_prime_UTR_variant	8/8	ENST00000250559.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAP1B	ENST00000250559.14	c.*11949C>T		3_prime_UTR_variant	8/8	1	NM_001010942.3	P1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34139 AN: 151670 Hom.: 4605 Cov.: 31

Gnomad AFR AF: 0.0880

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.250 AC: 3 AN: 12 Hom.: 1 Cov.: 0 AF XY: 0.250 AC XY: 2 AN XY: 8

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.225 AC: 34132 AN: 151786 Hom.: 4599 Cov.: 31 AF XY: 0.221 AC XY: 16425 AN XY: 74166

Gnomad4 AFR AF: 0.0877

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.214

Alfa AF: 0.288 Hom.: 7911

Bravo AF: 0.207

Asia WGS AF: 0.123 AC: 427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.4
Dann	Benign	0.70

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: rs11177325; hg19: chr12-69064978;