14-72472787-C-A

Variant names:

• chr14-72472787-C-A
• rs10131300
• NM_001204424.2:c.537-85C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001204424.2(RGS6):​c.537-85C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 979,808 control chromosomes in the GnomAD database, including 246,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (38324 hom., cov: 32)
  • Exomes 𝑓: 0.71 (208651 hom.)
• Consequence: RGS6 NM_001204424.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.144
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 14-72472787-C-A is Benign according to our data. Variant chr14-72472787-C-A is described in ClinVar as Benign. ClinVar VariationId is 1243968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204424.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS6	NM_001204424.2	MANE Select	c.537-85C>A		intron	N/A	NP_001191353.1
	RGS6	NM_001370275.1		c.537-85C>A		intron	N/A	NP_001357204.1
	RGS6	NM_001370276.1		c.537-85C>A		intron	N/A	NP_001357205.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS6	ENST00000553525.6	TSL:2 MANE Select	c.537-85C>A		intron	N/A	ENSP00000451030.1
	RGS6	ENST00000556437.5	TSL:1	c.537-85C>A		intron	N/A	ENSP00000451855.1
	RGS6	ENST00000404301.6	TSL:1	c.537-85C>A		intron	N/A	ENSP00000385243.2

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107417 AN: 151968 Hom.: 38295 Cov.: 32

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.702

GnomAD4 exome AF: 0.706 AC: 584278 AN: 827722 Hom.: 208651 AF XY: 0.707 AC XY: 305872 AN XY: 432922

African (AFR) AF: 0.713 AC: 13938 AN: 19550

American (AMR) AF: 0.837 AC: 28576 AN: 34132

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 13817 AN: 18328

East Asian (EAS) AF: 0.984 AC: 34499 AN: 35070

South Asian (SAS) AF: 0.764 AC: 47998 AN: 62790

European-Finnish (FIN) AF: 0.685 AC: 33780 AN: 49308

Middle Eastern (MID) AF: 0.736 AC: 3173 AN: 4312

European-Non Finnish (NFE) AF: 0.674 AC: 381238 AN: 565890

Other (OTH) AF: 0.711 AC: 27259 AN: 38342

GnomAD4 genome AF: 0.707 AC: 107495 AN: 152086 Hom.: 38324 Cov.: 32 AF XY: 0.713 AC XY: 53009 AN XY: 74346

African (AFR) AF: 0.703 AC: 29161 AN: 41464

American (AMR) AF: 0.774 AC: 11835 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2657 AN: 3466

East Asian (EAS) AF: 0.975 AC: 5055 AN: 5186

South Asian (SAS) AF: 0.773 AC: 3731 AN: 4824

European-Finnish (FIN) AF: 0.677 AC: 7162 AN: 10574

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45699 AN: 67970

Other (OTH) AF: 0.705 AC: 1489 AN: 2112

Alfa AF: 0.685 Hom.: 150624

Bravo AF: 0.716

Asia WGS AF: 0.844 AC: 2935 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jul 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.2
DANN	Benign	0.53
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10131300; hg19: chr14-72939495;