rs832358

Positions:

• chr2-107871445-A-G
• chr2-107871445-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0780

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]

LOC124906057 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
RGPD4	NM_182588.3	c.3441A>G	p.Leu1147Leu	synonymous_variant	20/23	ENST00000408999.4	NP_872394.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD4	ENST00000408999.4	c.3441A>G	p.Leu1147Leu	synonymous_variant	20/23	1	NM_182588.3	ENSP00000386810.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 6689 AN: 32558 Hom.: 1812 Cov.: 4 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

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.: 30 AF XY: 0.492 AC XY: 217879 AN XY: 442976

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.: 4 AF XY: 0.186 AC XY: 3013 AN XY: 16212

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

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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

Other links and lift over

dbSNP: rs832358; hg19: chr2-108487901; COSMIC: COSV61744327;