Variant 4-81447569-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_152545.3(RASGEF1B):c.664A>G(p.Asn222Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00223 in 1,613,832 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 40 hom. )

Consequence

RASGEF1B
NM_152545.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.94

Variant links:

Genes affected

RASGEF1B (HGNC:24881): (RasGEF domain family member 1B) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of catalytic activity and small GTPase mediated signal transduction. Predicted to be located in early endosome; late endosome; and midbody. [provided by Alliance of Genome Resources, Apr 2022]

RASGEF1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0074291527).

BP6

Variant 4-81447569-T-C is Benign according to our data. Variant chr4-81447569-T-C is described in ClinVar as [Benign]. Clinvar id is 3039822.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RASGEF1B	NM_152545.3 linkuse as main transcript	c.664A>G	p.Asn222Asp	missense_variant	6/14	ENST00000264400.7
RASGEF1B	NM_001300735.2 linkuse as main transcript	c.661A>G	p.Asn221Asp	missense_variant	6/14
RASGEF1B	NM_001300736.2 linkuse as main transcript	c.538A>G	p.Asn180Asp	missense_variant	5/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGEF1B	ENST00000264400.7 linkuse as main transcript	c.664A>G	p.Asn222Asp	missense_variant	6/14	2	NM_152545.3	A1	Q0VAM2-1

Frequencies

GnomAD3 genomes

AF:

0.00401

AC:

610

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0467

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00166

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00472

AC:

1187

AN:

251284

Hom.:

AF XY:

0.00457

AC XY:

621

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0444

Gnomad NFE exome

AF:

0.00181

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00205

AC:

2990

AN:

1461610

Hom.:

Cov.:

AF XY:

0.00194

AC XY:

1409

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0412

Gnomad4 NFE exome

AF:

0.000626

Gnomad4 OTH exome

AF:

0.00156

GnomAD4 genome

AF:

0.00401

AC:

610

AN:

152222

Hom.:

Cov.:

AF XY:

0.00569

AC XY:

423

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0467

Gnomad4 NFE

AF:

0.00166

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000935

Hom.:

Bravo

AF:

0.000427

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00352

AC:

428

EpiCase

AF:

0.000382

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

RASGEF1B-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Benign

-0.12

Eigen_PC

Benign

0.057

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D;D;D

MetaRNN

Benign

0.0074

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.6

N;N;.;N;N

REVEL

Benign

0.051

Sift

Uncertain

0.013

D;D;.;D;D

Sift4G

Uncertain

0.012

D;D;.;D;.

Polyphen

0.0080

B;B;.;B;.

Vest4

0.52

MVP

0.24

MPC

0.34

ClinPred

0.059

GERP RS

5.0

Varity_R

0.43

gMVP

0.29

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over