rs166370

Positions:

• chr1-240871393-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001364886.1(RGS7):​c.386-1274T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,988 control chromosomes in the GnomAD database, including 14,739 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 0.41 (14739 hom., cov: 32)
• Consequence: RGS7 NM_001364886.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152

Genes affected

RGS7 (HGNC:10003): (regulator of G protein signaling 7) Enables G-protein beta-subunit binding activity and GTPase activator activity. Involved in positive regulation of GTPase activity. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS7	NM_001364886.1	c.386-1274T>C		intron_variant		ENST00000440928.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS7	ENST00000440928.6	c.386-1274T>C		intron_variant		1	NM_001364886.1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61507 AN: 151870 Hom.: 14699 Cov.: 32

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.458

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.405 AC: 61592 AN: 151988 Hom.: 14739 Cov.: 32 AF XY: 0.398 AC XY: 29601 AN XY: 74298

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.379

Alfa AF: 0.332 Hom.: 17641

Bravo AF: 0.413

Asia WGS AF: 0.257 AC: 893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.5
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs166370; hg19: chr1-241034693;