14-72454709-C-G

Position:

• chr14-72454709-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001204424.2(RGS6):​c.235+131C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0601 in 643,506 control chromosomes in the GnomAD database, including 3,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1949 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1540 hom.)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0680

Genes affected

RGS6 (HGNC:10002): (regulator of G protein signaling 6) This gene encodes a member of the RGS (regulator of G protein signaling) family of proteins, which are defined by the presence of a RGS domain that confers the GTPase-activating activity of these proteins toward certain G alpha subunits. This protein also belongs to a subfamily of RGS proteins characterized by the presence of DEP and GGL domains, the latter a G beta 5-interacting domain. The RGS proteins negatively regulate G protein signaling, and may modulate neuronal, cardiovascular, lymphocytic activities, and cancer risk. Many alternatively spliced transcript variants encoding different isoforms with long or short N-terminal domains, complete or incomplete GGL domains, and distinct C-terminal domains, have been described for this gene, however, the full-length nature of some of these variants is not known.[provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 14-72454709-C-G is Benign according to our data. Variant chr14-72454709-C-G is described in ClinVar as [Benign]. Clinvar id is 1237670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS6	NM_001204424.2	c.235+131C>G		intron_variant		ENST00000553525.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS6	ENST00000553525.6	c.235+131C>G		intron_variant		2	NM_001204424.2	P1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16193 AN: 152012 Hom.: 1935 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.0708

Gnomad SAS AF: 0.0946

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.0881

GnomAD4 exome AF: 0.0457 AC: 22438 AN: 491376 Hom.: 1540 AF XY: 0.0458 AC XY: 11824 AN XY: 258174

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.184

Gnomad4 ASJ exome AF: 0.0195

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.0964

Gnomad4 FIN exome AF: 0.0310

Gnomad4 NFE exome AF: 0.0135

Gnomad4 OTH exome AF: 0.0532

GnomAD4 genome AF: 0.107 AC: 16265 AN: 152130 Hom.: 1949 Cov.: 32 AF XY: 0.108 AC XY: 8012 AN XY: 74376

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.0706

Gnomad4 SAS AF: 0.0936

Gnomad4 FIN AF: 0.0344

Gnomad4 NFE AF: 0.0133

Gnomad4 OTH AF: 0.0882

Alfa AF: 0.0187 Hom.: 26

Bravo AF: 0.124

Asia WGS AF: 0.112 AC: 390 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 21, 2018	- -
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	-0.83
CADD	Benign	4.0
DANN	Benign	0.47

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: rs2302144; hg19: chr14-72921417;