rs10516428

Variant names:

• chr4-98316288-T-G
• rs10516428
• NM_001100427.2:c.112+22773T>G

Variant summary

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

The NM_001100427.2(RAP1GDS1):​c.112+22773T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,312 control chromosomes in the GnomAD database, including 16,188 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 0.41 (16188 hom., cov: 31)
• Consequence: RAP1GDS1 NM_001100427.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 9 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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAP1GDS1	NM_001100427.2	c.112+22773T>G		intron_variant	Intron 2 of 14	ENST00000408927.8	NP_001093897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAP1GDS1	ENST00000408927.8	c.112+22773T>G		intron_variant	Intron 2 of 14	2	NM_001100427.2	ENSP00000386153.4

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62356 AN: 151194 Hom.: 16128 Cov.: 31

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.423

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.398

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.413 AC: 62472 AN: 151312 Hom.: 16188 Cov.: 31 AF XY: 0.415 AC XY: 30638 AN XY: 73882

African (AFR) AF: 0.743 AC: 30735 AN: 41358

American (AMR) AF: 0.378 AC: 5744 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 991 AN: 3452

East Asian (EAS) AF: 0.323 AC: 1650 AN: 5112

South Asian (SAS) AF: 0.411 AC: 1966 AN: 4780

European-Finnish (FIN) AF: 0.281 AC: 2940 AN: 10454

Middle Eastern (MID) AF: 0.424 AC: 123 AN: 290

European-Non Finnish (NFE) AF: 0.253 AC: 17144 AN: 67668

Other (OTH) AF: 0.398 AC: 839 AN: 2110

Alfa AF: 0.307 Hom.: 32668

Bravo AF: 0.435

Asia WGS AF: 0.444 AC: 1543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.2
DANN	Benign	0.77
PhyloP100		0.062
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: rs10516428; hg19: chr4-99237439;