4-98356800-G-C

Position:

• chr4-98356800-G-C

Variant summary

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

The NM_001100427.2(RAP1GDS1):​c.361+4199G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 151,982 control chromosomes in the GnomAD database, including 396 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 0.046 (396 hom., cov: 32)
• Consequence: RAP1GDS1 NM_001100427.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.829

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAP1GDS1	NM_001100427.2	c.361+4199G>C		intron_variant		ENST00000408927.8	NP_001093897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAP1GDS1	ENST00000408927.8	c.361+4199G>C		intron_variant		2	NM_001100427.2	ENSP00000386153	A1

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6951 AN: 151864 Hom.: 393 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.0214

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0413

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

GnomAD4 genome AF: 0.0459 AC: 6972 AN: 151982 Hom.: 396 Cov.: 32 AF XY: 0.0440 AC XY: 3267 AN XY: 74298

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0243

Gnomad4 ASJ AF: 0.0214

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0170

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.0409

Alfa AF: 0.00475 Hom.: 3

Bravo AF: 0.0514

Asia WGS AF: 0.0140 AC: 50 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.68

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: rs41525749; hg19: chr4-99277951;