dbSNP rs832358: RGPD4:p.Leu1147Leu (chr2-107871445-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_182588.3(RGPD4):c.3441A>G(p.Leu1147Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 1825 hom., cov: 4)

Exomes 𝑓: 0.48 ( 207130 hom. )

Failed GnomAD Quality Control

Consequence

RGPD4
NM_182588.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0780

Variant links:

Genes affected

RGPD4 (HGNC:32417): (RANBP2 like and GRIP domain containing 4) Predicted to contribute to GTPase activator activity. Predicted to be involved in NLS-bearing protein import into nucleus. Predicted to be part of nuclear pore. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RGPD4 links:

LOC124906057 (HGNC:):

LOC124906057 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 2-107871445-A-G is Benign according to our data. Variant chr2-107871445-A-G is described in ClinVar as [Benign]. Clinvar id is 403374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.078 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGPD4	NM_182588.3 link	c.3441A>G	p.Leu1147Leu	synonymous_variant	Exon 20 of 23	ENST00000408999.4	NP_872394.2	Q7Z3J3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGPD4	ENST00000408999.4 link	c.3441A>G	p.Leu1147Leu	synonymous_variant	Exon 20 of 23	1	NM_182588.3	ENSP00000386810.4		Q7Z3J3-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

6689

AN:

32558

Hom.:

1812

Cov.:

FAILED QC

Gnomad AFR

AF:

0.416

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.105

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.250

GnomAD3 exomes

AF:

0.215

AC:

28750

AN:

133662

Hom.:

14070

AF XY:

0.205

AC XY:

14389

AN XY:

70126

show subpopulations

Gnomad AFR exome

AF:

0.683

Gnomad AMR exome

AF:

0.159

Gnomad ASJ exome

AF:

0.228

Gnomad EAS exome

AF:

0.0632

Gnomad SAS exome

AF:

0.319

Gnomad FIN exome

AF:

0.0503

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.293

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.480

AC:

426449

AN:

888328

Hom.:

207130

Cov.:

AF XY:

0.492

AC XY:

217879

AN XY:

442976

show subpopulations

Gnomad4 AFR exome

AF:

0.817

Gnomad4 AMR exome

AF:

0.298

Gnomad4 ASJ exome

AF:

0.675

Gnomad4 EAS exome

AF:

0.225

Gnomad4 SAS exome

AF:

0.692

Gnomad4 FIN exome

AF:

0.572

Gnomad4 NFE exome

AF:

0.460

Gnomad4 OTH exome

AF:

0.560

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.206

AC:

6702

AN:

32568

Hom.:

1825

Cov.:

AF XY:

0.186

AC XY:

3013

AN XY:

16212

show subpopulations

Gnomad4 AFR

AF:

0.419

Gnomad4 AMR

AF:

0.166

Gnomad4 ASJ

AF:

0.228

Gnomad4 EAS

AF:

0.106

Gnomad4 SAS

AF:

0.340

Gnomad4 FIN

AF:

0.105

Gnomad4 NFE

AF:

0.184

Gnomad4 OTH

AF:

0.248

Alfa

AF:

0.383

Hom.:

909

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

6.9

DANN

Benign

0.58

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