Genetic Variant RGSL1:p.Arg245Arg (chr1-182473846-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001137669.2(RGSL1):c.735G>A(p.Arg245Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,551,682 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 12 hom. )

Consequence

RGSL1
NM_001137669.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.346

Variant links:

Genes affected

RGSL1 (HGNC:18636): (regulator of G protein signaling like 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

RGSL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-182473846-G-A is Benign according to our data. Variant chr1-182473846-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2639618.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.346 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00133 (1860/1399456) while in subpopulation MID AF= 0.0274 (156/5698). AF 95% confidence interval is 0.0239. There are 12 homozygotes in gnomad4_exome. There are 936 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGSL1	NM_001137669.2 link	c.735G>A	p.Arg245Arg	synonymous_variant	Exon 6 of 22	ENST00000294854.13	NP_001131141.1	A5PLK6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGSL1	ENST00000294854.13 link	c.735G>A	p.Arg245Arg	synonymous_variant	Exon 6 of 22	1	NM_001137669.2	ENSP00000457748.1		A5PLK6-1

Frequencies

GnomAD3 genomes

AF:

0.00159

AC:

242

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00187

AC:

296

AN:

158130

Hom.:

AF XY:

0.00176

AC XY:

146

AN XY:

83104

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00356

Gnomad ASJ exome

AF:

0.00801

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000527

Gnomad FIN exome

AF:

0.0000590

Gnomad NFE exome

AF:

0.00168

Gnomad OTH exome

AF:

0.00559

GnomAD4 exome

AF:

0.00133

AC:

1860

AN:

1399456

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

936

AN XY:

690242

show subpopulations

Gnomad4 AFR exome

AF:

0.00101

Gnomad4 AMR exome

AF:

0.00378

Gnomad4 ASJ exome

AF:

0.00862

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.000442

Gnomad4 FIN exome

AF:

0.0000406

Gnomad4 NFE exome

AF:

0.000994

Gnomad4 OTH exome

AF:

0.00362

GnomAD4 genome

AF:

0.00158

AC:

241

AN:

152226

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000458

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.00864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00175

Hom.:

Bravo

AF:

0.00175

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RGSL1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.3

DANN

Benign

0.54

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