chr4-98356800-G-C

Variant names:

• chr4-98356800-G-C
• rs41525749
• NM_001100427.2:c.361+4199G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1GDS1	NM_001100427.2	MANE Select	c.361+4199G>C		intron	N/A	NP_001093897.1
	RAP1GDS1	NM_001100426.2		c.364+4199G>C		intron	N/A	NP_001093896.1
	RAP1GDS1	NM_021159.5		c.364+4199G>C		intron	N/A	NP_066982.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAP1GDS1	ENST00000408927.8	TSL:2 MANE Select	c.361+4199G>C		intron	N/A	ENSP00000386153.4
	RAP1GDS1	ENST00000339360.9	TSL:1	c.364+4199G>C		intron	N/A	ENSP00000340454.5
	RAP1GDS1	ENST00000453712.6	TSL:1	c.364+4199G>C		intron	N/A	ENSP00000407157.2

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

African (AFR) AF: 0.134 AC: 5560 AN: 41510

American (AMR) AF: 0.0243 AC: 371 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0214 AC: 74 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.0170 AC: 82 AN: 4822

European-Finnish (FIN) AF: 0.00217 AC: 23 AN: 10610

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0112 AC: 761 AN: 67802

Other (OTH) AF: 0.0409 AC: 86 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.68
PhyloP100		-0.83
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: rs41525749; hg19: chr4-99277951;