chr14-71925485-A-G

Variant names:

• chr14-71925485-A-G
• rs36339
• ENST00000555581.2:n.682-2798A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000555581.2(ENSG00000266869):​n.682-2798A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0658 in 152,186 control chromosomes in the GnomAD database, including 404 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.066 (404 hom., cov: 32)
• Consequence: ENSG00000266869 ENST00000555581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209
• Publications: 1 publications found

Genes affected

ENSG00000266869 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.089 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000555581.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000266869	ENST00000555581.2	TSL:5	n.682-2798A>G		intron	N/A
	ENSG00000266869	ENST00000655301.1		n.842-2798A>G		intron	N/A
	ENSG00000266869	ENST00000656145.1		n.963-2798A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0659 AC: 10017 AN: 152068 Hom.: 404 Cov.: 32

Gnomad AFR AF: 0.0341

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.0744

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.00732

Gnomad SAS AF: 0.0265

Gnomad FIN AF: 0.0440

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0908

Gnomad OTH AF: 0.0834

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

GnomAD4 genome AF: 0.0658 AC: 10007 AN: 152186 Hom.: 404 Cov.: 32 AF XY: 0.0621 AC XY: 4624 AN XY: 74404

African (AFR) AF: 0.0340 AC: 1412 AN: 41536

American (AMR) AF: 0.0741 AC: 1132 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0767 AC: 266 AN: 3470

East Asian (EAS) AF: 0.00734 AC: 38 AN: 5176

South Asian (SAS) AF: 0.0259 AC: 125 AN: 4824

European-Finnish (FIN) AF: 0.0440 AC: 466 AN: 10590

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0908 AC: 6177 AN: 67994

Other (OTH) AF: 0.0830 AC: 175 AN: 2108

Alfa AF: 0.0712 Hom.: 57

Bravo AF: 0.0688

Asia WGS AF: 0.0170 AC: 62 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.81
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs36339; hg19: chr14-72392202;