4-98352484-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001100427.2(RAP1GDS1):c.244C>A(p.Arg82=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00548 in 1,612,784 control chromosomes in the GnomAD database, including 337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (166 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (171 hom.)
• Consequence: RAP1GDS1 NM_001100427.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.89

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).
• BP6: Variant 4-98352484-C-A is Benign according to our data. Variant chr4-98352484-C-A is described in ClinVar as [Benign]. Clinvar id is 786041.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.89 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAP1GDS1	NM_001100427.2	c.244C>A	p.Arg82=	synonymous_variant	4/15	ENST00000408927.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAP1GDS1	ENST00000408927.8	c.244C>A	p.Arg82=	synonymous_variant	4/15	2	NM_001100427.2	A1

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3929 AN: 152034 Hom.: 164 Cov.: 32

Gnomad AFR AF: 0.0876

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.0239

GnomAD3 exomes AF: 0.00725 AC: 1805 AN: 248952 Hom.: 73 AF XY: 0.00560 AC XY: 757 AN XY: 135066

Gnomad AFR exome AF: 0.0936

Gnomad AMR exome AF: 0.00585

Gnomad ASJ exome AF: 0.000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000526

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000911

Gnomad OTH exome AF: 0.00480

GnomAD4 exome AF: 0.00335 AC: 4889 AN: 1460632 Hom.: 171 Cov.: 30 AF XY: 0.00305 AC XY: 2219 AN XY: 726604

Gnomad4 AFR exome AF: 0.0968

Gnomad4 AMR exome AF: 0.00685

Gnomad4 ASJ exome AF: 0.00103

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000465

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000634

Gnomad4 OTH exome AF: 0.00814

GnomAD4 genome AF: 0.0259 AC: 3948 AN: 152152 Hom.: 166 Cov.: 32 AF XY: 0.0254 AC XY: 1886 AN XY: 74394

Gnomad4 AFR AF: 0.0878

Gnomad4 AMR AF: 0.0126

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000794

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.00872 Hom.: 25

Bravo AF: 0.0301

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.00109

EpiControl AF: 0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 24, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
Cadd	Benign	11
Dann	Benign	0.94

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: rs61758756; hg19: chr4-99273635;