14-71964493-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001204424.2(RGS6):c.-20-279C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 151,932 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.013 (20 hom., cov: 33)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.538

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 14-71964493-C-T is Benign according to our data. Variant chr14-71964493-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1318175.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0135 (2045/151932) while in subpopulation NFE AF= 0.021 (1426/67958). AF 95% confidence interval is 0.0201. There are 20 homozygotes in gnomad4. There are 925 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 2045 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS6	NM_001204424.2	c.-20-279C>T		intron_variant		ENST00000553525.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS6	ENST00000553525.6	c.-20-279C>T		intron_variant		2	NM_001204424.2	P1

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2045 AN: 151814 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.00423

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0210

Gnomad OTH AF: 0.0168

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0135 AC: 2045 AN: 151932 Hom.: 20 Cov.: 33 AF XY: 0.0125 AC XY: 925 AN XY: 74202

Gnomad4 AFR AF: 0.00422

Gnomad4 AMR AF: 0.0136

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00333

Gnomad4 FIN AF: 0.0153

Gnomad4 NFE AF: 0.0210

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.0167 Hom.: 3

Bravo AF: 0.0131

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.30
Dann	Benign	0.56

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: rs140930318; hg19: chr14-72431210;