Variant 9-133101589-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The ENST00000372050.8(RALGDS):c.2385G>A(p.Gln795=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00486 in 1,612,878 control chromosomes in the GnomAD database, including 205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 14 hom., cov: 34)

Exomes 𝑓: 0.0050 ( 191 hom. )

Consequence

RALGDS
ENST00000372050.8 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.37

Variant links:

Genes affected

RALGDS (HGNC:9842): (ral guanine nucleotide dissociation stimulator) Guanine nucleotide dissociation stimulators (GDSs, or exchange factors), such as RALGDS, are effectors of Ras-related GTPases (see MIM 190020) that participate in signaling for a variety of cellular processes.[supplied by OMIM, Nov 2010]

RALGDS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 9-133101589-C-T is Benign according to our data. Variant chr9-133101589-C-T is described in ClinVar as [Benign]. Clinvar id is 775280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.37 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00356 (542/152372) while in subpopulation SAS AF= 0.048 (232/4830). AF 95% confidence interval is 0.043. There are 14 homozygotes in gnomad4. There are 334 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 542 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RALGDS	NM_006266.4 linkuse as main transcript	c.2385G>A	p.Gln795=	synonymous_variant	16/18	ENST00000372050.8	NP_006257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RALGDS	ENST00000372050.8 linkuse as main transcript	c.2385G>A	p.Gln795=	synonymous_variant	16/18	1	NM_006266.4	ENSP00000361120	A2	Q12967-1

Frequencies

GnomAD3 genomes

AF:

0.00353

AC:

538

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000699

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00606

Gnomad EAS

AF:

0.0281

Gnomad SAS

AF:

0.0482

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00907

AC:

2263

AN:

249562

Hom.:

AF XY:

0.0112

AC XY:

1518

AN XY:

135198

show subpopulations

Gnomad AFR exome

AF:

0.000802

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00547

Gnomad EAS exome

AF:

0.0271

Gnomad SAS exome

AF:

0.0481

Gnomad FIN exome

AF:

0.0000489

Gnomad NFE exome

AF:

0.00136

Gnomad OTH exome

AF:

0.00524

GnomAD4 exome

AF:

0.00500

AC:

7301

AN:

1460506

Hom.:

191

Cov.:

AF XY:

0.00658

AC XY:

4783

AN XY:

726626

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.00719

Gnomad4 EAS exome

AF:

0.0363

Gnomad4 SAS exome

AF:

0.0496

Gnomad4 FIN exome

AF:

0.0000384

Gnomad4 NFE exome

AF:

0.000758

Gnomad4 OTH exome

AF:

0.00684

GnomAD4 genome

AF:

0.00356

AC:

542

AN:

152372

Hom.:

Cov.:

AF XY:

0.00448

AC XY:

334

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000697

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00606

Gnomad4 EAS

AF:

0.0279

Gnomad4 SAS

AF:

0.0480

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00125

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00180

Hom.:

Bravo

AF:

0.00237

Asia WGS

AF:

0.0430

AC:

149

AN:

3478

EpiCase

AF:

0.00207

EpiControl

AF:

0.00207

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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