Variant 4-81440911-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152545.3(RASGEF1B):c.1027A>G(p.Ser343Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000241 in 1,611,198 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

RASGEF1B
NM_152545.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.64

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17695826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RASGEF1B	NM_152545.3 linkuse as main transcript	c.1027A>G	p.Ser343Gly	missense_variant	10/14	ENST00000264400.7
RASGEF1B	NM_001300735.2 linkuse as main transcript	c.1024A>G	p.Ser342Gly	missense_variant	10/14
RASGEF1B	NM_001300736.2 linkuse as main transcript	c.901A>G	p.Ser301Gly	missense_variant	9/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASGEF1B	ENST00000264400.7 linkuse as main transcript	c.1027A>G	p.Ser343Gly	missense_variant	10/14	2	NM_152545.3	A1	Q0VAM2-1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000151

AC:

AN:

251030

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.000326

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000244

AC:

356

AN:

1458992

Hom.:

Cov.:

AF XY:

0.000219

AC XY:

159

AN XY:

725998

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000309

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000217

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000452

Hom.:

Bravo

AF:

0.000170

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 24, 2023

The c.1027A>G (p.S343G) alteration is located in exon 10 (coding exon 9) of the RASGEF1B gene. This alteration results from a A to G substitution at nucleotide position 1027, causing the serine (S) at amino acid position 343 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.29

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.21

Eigen_PC

Benign

0.0061

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.86

D;D;D;D;D

M_CAP

Benign

0.0075

MetaRNN

Benign

0.18

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.7

N;N;.;N;N

REVEL

Benign

0.11

Sift

Benign

0.33

T;T;.;T;T

Sift4G

Benign

0.32

T;T;.;T;.

Polyphen

0.0070

B;B;.;B;.

Vest4

0.34

MVP

0.34

MPC

0.27

ClinPred

0.097

GERP RS

5.2

Varity_R

0.31

gMVP

0.38

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