rs11177325

Variant names:

• chr12-68671198-C-T
• rs11177325
• NM_001010942.3:c.*11949C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

RAP1B Gene-Disease associations (from GenCC):

• thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, G2P
• syndromic constitutional thrombocytopenia

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAP1B	NM_001010942.3	c.*11949C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000250559.14	NP_001010942.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAP1B	ENST00000250559.14	c.*11949C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_001010942.3	ENSP00000250559.9

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.0877 AC: 3631 AN: 41384

American (AMR) AF: 0.182 AC: 2771 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 739 AN: 3468

East Asian (EAS) AF: 0.120 AC: 619 AN: 5166

South Asian (SAS) AF: 0.116 AC: 559 AN: 4804

European-Finnish (FIN) AF: 0.341 AC: 3579 AN: 10492

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.315 AC: 21428 AN: 67922

Other (OTH) AF: 0.214 AC: 449 AN: 2094

Alfa AF: 0.279 Hom.: 10298

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
PhyloP100		-0.32

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

Other links and lift over

dbSNP: rs11177325; hg19: chr12-69064978;