rs10516430

Variant names:

• chr4-98416730-C-T
• rs10516430
• NM_001100427.2:c.764-15C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001100427.2(RAP1GDS1):​c.764-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,573,948 control chromosomes in the GnomAD database, including 60,736 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 0.24 (4577 hom., cov: 31)
  • Exomes 𝑓: 0.28 (56159 hom.)
• Consequence: RAP1GDS1 NM_001100427.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.426
• Publications: 20 publications found

Genes affected

RAP1GDS1 (HGNC:9859): (Rap1 GTPase-GDP dissociation stimulator 1) The smg GDP dissociation stimulator (smgGDS) protein is a stimulatory GDP/GTP exchange protein with GTPase activity (Riess et al., 1993 [PubMed 8262526]).[supplied by OMIM, Feb 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100427.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1GDS1	NM_001100427.2	MANE Select	c.764-15C>T		intron	N/A	NP_001093897.1	P52306-1
	RAP1GDS1	NM_001100426.2		c.767-15C>T		intron	N/A	NP_001093896.1	P52306-5
	RAP1GDS1	NM_021159.5		c.767-15C>T		intron	N/A	NP_066982.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1GDS1	ENST00000408927.8	TSL:2 MANE Select	c.764-15C>T		intron	N/A	ENSP00000386153.4	P52306-1
	RAP1GDS1	ENST00000339360.9	TSL:1	c.767-15C>T		intron	N/A	ENSP00000340454.5	P52306-5
	RAP1GDS1	ENST00000453712.6	TSL:1	c.767-15C>T		intron	N/A	ENSP00000407157.2	P52306-4

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36221 AN: 151736 Hom.: 4576 Cov.: 31

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.260

GnomAD2 exomes AF: 0.260 AC: 63341 AN: 243210 AF XY: 0.268

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.172

Gnomad ASJ exome AF: 0.285

Gnomad EAS exome AF: 0.273

Gnomad FIN exome AF: 0.283

Gnomad NFE exome AF: 0.284

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.279 AC: 396122 AN: 1422094 Hom.: 56159 Cov.: 30 AF XY: 0.280 AC XY: 198508 AN XY: 709394

African (AFR) AF: 0.142 AC: 4592 AN: 32236

American (AMR) AF: 0.177 AC: 7547 AN: 42582

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 7085 AN: 25472

East Asian (EAS) AF: 0.230 AC: 9091 AN: 39456

South Asian (SAS) AF: 0.297 AC: 25104 AN: 84552

European-Finnish (FIN) AF: 0.279 AC: 14798 AN: 53078

Middle Eastern (MID) AF: 0.256 AC: 1444 AN: 5638

European-Non Finnish (NFE) AF: 0.287 AC: 310334 AN: 1080052

Other (OTH) AF: 0.273 AC: 16127 AN: 59028

GnomAD4 genome AF: 0.239 AC: 36222 AN: 151854 Hom.: 4577 Cov.: 31 AF XY: 0.239 AC XY: 17720 AN XY: 74194

African (AFR) AF: 0.152 AC: 6273 AN: 41398

American (AMR) AF: 0.209 AC: 3190 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 946 AN: 3462

East Asian (EAS) AF: 0.267 AC: 1377 AN: 5162

South Asian (SAS) AF: 0.304 AC: 1466 AN: 4816

European-Finnish (FIN) AF: 0.291 AC: 3055 AN: 10504

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18966 AN: 67946

Other (OTH) AF: 0.259 AC: 548 AN: 2114

Alfa AF: 0.268 Hom.: 20425

Bravo AF: 0.230

Asia WGS AF: 0.324 AC: 1123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.82
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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: rs10516430; hg19: chr4-99337881; COSMIC: COSV52787213;