chr14-72562470-G-A

Variant names:

• chr14-72562470-G-A
• rs2074647
• ENST00000554474.5:n.*141G>A

Variant summary

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

The ENST00000554474.5(RGS6):​n.*141G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0889 in 1,612,136 control chromosomes in the GnomAD database, including 6,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (838 hom., cov: 32)
  • Exomes 𝑓: 0.088 (5940 hom.)
• Consequence: RGS6 ENST00000554474.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.42
• Publications: 13 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]

ENSG00000258871 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016974509).
• BP6: Variant 14-72562470-G-A is Benign according to our data. Variant chr14-72562470-G-A is described in ClinVar as Benign. ClinVar VariationId is 1258962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS6	NM_001204424.2	c.*3G>A		3_prime_UTR_variant	Exon 18 of 18	ENST00000553525.6	NP_001191353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS6	ENST00000553525.6	c.*3G>A		3_prime_UTR_variant	Exon 18 of 18	2	NM_001204424.2	ENSP00000451030.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15434 AN: 152178 Hom.: 837 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0907

Gnomad EAS AF: 0.0651

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0544

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.0902

Gnomad OTH AF: 0.0913

GnomAD2 exomes AF: 0.0902 AC: 22398 AN: 248360 AF XY: 0.0911

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.0872

Gnomad ASJ exome AF: 0.0880

Gnomad EAS exome AF: 0.0609

Gnomad FIN exome AF: 0.0526

Gnomad NFE exome AF: 0.0917

Gnomad OTH exome AF: 0.100

GnomAD4 exome AF: 0.0876 AC: 127881 AN: 1459840 Hom.: 5940 Cov.: 32 AF XY: 0.0887 AC XY: 64404 AN XY: 726334

African (AFR) AF: 0.134 AC: 4502 AN: 33476

American (AMR) AF: 0.0888 AC: 3973 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 2296 AN: 26136

East Asian (EAS) AF: 0.0864 AC: 3430 AN: 39698

South Asian (SAS) AF: 0.105 AC: 9099 AN: 86252

European-Finnish (FIN) AF: 0.0571 AC: 2936 AN: 51448

Middle Eastern (MID) AF: 0.150 AC: 864 AN: 5768

European-Non Finnish (NFE) AF: 0.0855 AC: 95110 AN: 1111972

Other (OTH) AF: 0.0939 AC: 5671 AN: 60374

GnomAD4 genome AF: 0.101 AC: 15448 AN: 152296 Hom.: 838 Cov.: 32 AF XY: 0.0996 AC XY: 7420 AN XY: 74464

African (AFR) AF: 0.132 AC: 5490 AN: 41562

American (AMR) AF: 0.110 AC: 1681 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0907 AC: 315 AN: 3472

East Asian (EAS) AF: 0.0649 AC: 336 AN: 5180

South Asian (SAS) AF: 0.105 AC: 507 AN: 4826

European-Finnish (FIN) AF: 0.0544 AC: 578 AN: 10620

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.0902 AC: 6134 AN: 68020

Other (OTH) AF: 0.0913 AC: 193 AN: 2114

Alfa AF: 0.0953 Hom.: 1713

Bravo AF: 0.106

TwinsUK AF: 0.0871 AC: 323

ALSPAC AF: 0.0799 AC: 308

ESP6500AA AF: 0.140 AC: 619

ESP6500EA AF: 0.0917 AC: 789

ExAC AF: 0.0922 AC: 11193

Asia WGS AF: 0.0960 AC: 337 AN: 3478

EpiCase AF: 0.0987

EpiControl AF: 0.0996

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

- -

Apr 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 15375002) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.91
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0017	T
PhyloP100		3.4
GERP RS		3.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2074647; hg19: chr14-73029178;