rs4659583

chr1-240876222-T-C

Variant summary

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

The NM_001364886.1(RGS7):c.386-6103A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,858 control chromosomes in the GnomAD database, including 24,376 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 0.56 (24376 hom., cov: 31)
• Consequence: RGS7 NM_001364886.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) 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.386-6103A>G		intron_variant		ENST00000440928.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS7	ENST00000440928.6	c.386-6103A>G		intron_variant		1	NM_001364886.1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84618 AN: 151738 Hom.: 24363 Cov.: 31

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.558 AC: 84673 AN: 151858 Hom.: 24376 Cov.: 31 AF XY: 0.559 AC XY: 41458 AN XY: 74200

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.565

Alfa AF: 0.563 Hom.: 4861

Bravo AF: 0.547

Asia WGS AF: 0.626 AC: 2180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	4.2
Dann	Benign	0.41

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: rs4659583; hg19: chr1-241039522;