Variant 20-38499437-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_020336.4(RALGAPB):c.554-10T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 1,567,000 control chromosomes in the GnomAD database, including 976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.049 ( 348 hom., cov: 32)

Exomes 𝑓: 0.022 ( 628 hom. )

Consequence

RALGAPB
NM_020336.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.003213

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0550

Variant links:

Genes affected

RALGAPB (HGNC:29221): (Ral GTPase activating protein non-catalytic subunit beta) Enables protein heterodimerization activity. Predicted to be involved in activation of GTPase activity. Predicted to act upstream of or within Ral protein signal transduction; regulation of exocyst localization; and regulation of protein localization. [provided by Alliance of Genome Resources, Apr 2022]

RALGAPB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 20-38499437-T-C is Benign according to our data. Variant chr20-38499437-T-C is described in ClinVar as [Benign]. Clinvar id is 3055608.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RALGAPB	NM_020336.4 linkuse as main transcript	c.554-10T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000262879.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RALGAPB	ENST00000262879.11 linkuse as main transcript	c.554-10T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_020336.4	P4	Q86X10-1

Frequencies

GnomAD3 genomes

AF:

0.0491

AC:

7468

AN:

152194

Hom.:

345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0266

Gnomad ASJ

AF:

0.0628

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.00786

Gnomad FIN

AF:

0.00583

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0204

Gnomad OTH

AF:

0.0435

GnomAD3 exomes

AF:

0.0241

AC:

5327

AN:

220648

Hom.:

154

AF XY:

0.0214

AC XY:

2568

AN XY:

120212

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.0165

Gnomad ASJ exome

AF:

0.0517

Gnomad EAS exome

AF:

0.00369

Gnomad SAS exome

AF:

0.00730

Gnomad FIN exome

AF:

0.00595

Gnomad NFE exome

AF:

0.0201

Gnomad OTH exome

AF:

0.0314

GnomAD4 exome

AF:

0.0216

AC:

30570

AN:

1414688

Hom.:

628

Cov.:

AF XY:

0.0211

AC XY:

14771

AN XY:

701324

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.0179

Gnomad4 ASJ exome

AF:

0.0528

Gnomad4 EAS exome

AF:

0.00154

Gnomad4 SAS exome

AF:

0.00727

Gnomad4 FIN exome

AF:

0.00684

Gnomad4 NFE exome

AF:

0.0197

Gnomad4 OTH exome

AF:

0.0286

GnomAD4 genome

AF:

0.0491

AC:

7486

AN:

152312

Hom.:

348

Cov.:

AF XY:

0.0472

AC XY:

3518

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.0265

Gnomad4 ASJ

AF:

0.0628

Gnomad4 EAS

AF:

0.00328

Gnomad4 SAS

AF:

0.00766

Gnomad4 FIN

AF:

0.00583

Gnomad4 NFE

AF:

0.0204

Gnomad4 OTH

AF:

0.0431

Alfa

AF:

0.0292

Hom.:

153

Bravo

AF:

0.0547

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

RALGAPB-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 18, 2020

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

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.64

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0032

dbscSNV1_RF

Benign

0.20

SpliceAI score (max)

0.070

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