14-71964738-C-T

Position:

• chr14-71964738-C-T

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.-20-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00357 in 1,439,510 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (73 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (61 hom.)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.613

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]

RGS6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 14-71964738-C-T is Benign according to our data. Variant chr14-71964738-C-T is described in ClinVar as [Benign]. Clinvar id is 1244827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.056 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS6	NM_001204424.2	c.-20-34C>T		intron_variant		ENST00000553525.6	NP_001191353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS6	ENST00000553525.6	c.-20-34C>T		intron_variant		2	NM_001204424.2	ENSP00000451030.1

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2612 AN: 152126 Hom.: 74 Cov.: 33

Gnomad AFR AF: 0.0577

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00982

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.00195 AC: 2513 AN: 1287266 Hom.: 61 Cov.: 17 AF XY: 0.00180 AC XY: 1160 AN XY: 644088

Gnomad4 AFR exome AF: 0.0588

Gnomad4 AMR exome AF: 0.00466

Gnomad4 ASJ exome AF: 0.000129

Gnomad4 EAS exome AF: 0.0000531

Gnomad4 SAS exome AF: 0.000324

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000285

Gnomad4 OTH exome AF: 0.00543

GnomAD4 genome AF: 0.0172 AC: 2626 AN: 152244 Hom.: 73 Cov.: 33 AF XY: 0.0160 AC XY: 1191 AN XY: 74448

Gnomad4 AFR AF: 0.0579

Gnomad4 AMR AF: 0.00981

Gnomad4 ASJ AF: 0.000866

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000515

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.0145 Hom.: 5

Bravo AF: 0.0197

Asia WGS AF: 0.00693 AC: 24 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 06, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.75

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: rs77884502; hg19: chr14-72431455;