14-71964882-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001204424.2(RGS6):c.84+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0066 in 1,611,602 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0068 (31 hom.)
• Consequence: RGS6 NM_001204424.2 splice_region, intron
• Scores: Splicing: ADA: 0.0003081
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.12

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 14-71964882-C-T is Benign according to our data. Variant chr14-71964882-C-T is described in ClinVar as [Benign]. Clinvar id is 784289.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 751 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS6	NM_001204424.2	c.84+7C>T		splice_region_variant, intron_variant		ENST00000553525.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS6	ENST00000553525.6	c.84+7C>T		splice_region_variant, intron_variant		2	NM_001204424.2	P1

Frequencies

GnomAD3 genomes AF: 0.00494 AC: 751 AN: 152136 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.00491

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00801

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00507 AC: 1270 AN: 250618 Hom.: 7 AF XY: 0.00508 AC XY: 688 AN XY: 135452

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00381

Gnomad ASJ exome AF: 0.000796

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00190

Gnomad FIN exome AF: 0.00366

Gnomad NFE exome AF: 0.00824

Gnomad OTH exome AF: 0.00607

GnomAD4 exome AF: 0.00678 AC: 9890 AN: 1459348 Hom.: 31 Cov.: 29 AF XY: 0.00654 AC XY: 4752 AN XY: 726136

Gnomad4 AFR exome AF: 0.000988

Gnomad4 AMR exome AF: 0.00388

Gnomad4 ASJ exome AF: 0.000881

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00173

Gnomad4 FIN exome AF: 0.00371

Gnomad4 NFE exome AF: 0.00808

Gnomad4 OTH exome AF: 0.00576

GnomAD4 genome AF: 0.00492 AC: 749 AN: 152254 Hom.: 1 Cov.: 33 AF XY: 0.00446 AC XY: 332 AN XY: 74446

Gnomad4 AFR AF: 0.00128

Gnomad4 AMR AF: 0.00491

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000830

Gnomad4 FIN AF: 0.00358

Gnomad4 NFE AF: 0.00801

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00522 Hom.: 2

Bravo AF: 0.00528

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00753

EpiControl AF: 0.00718

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 05, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	10
Dann	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00031
dbscSNV1_RF	Benign	0.0060
SpliceAI score (max)		0.49		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.49		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61755651; hg19: chr14-72431599; COSMIC: COSV105904404;