rs4659583

Variant names:

• chr1-240876222-T-C
• rs4659583
• NM_001364886.1:c.386-6103A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

RGS7 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RGS7	NM_001364886.1	c.386-6103A>G		intron_variant	Intron 6 of 18	ENST00000440928.6	NP_001351815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS7	ENST00000440928.6	c.386-6103A>G		intron_variant	Intron 6 of 18	1	NM_001364886.1	ENSP00000404399.2

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

African (AFR) AF: 0.407 AC: 16836 AN: 41408

American (AMR) AF: 0.546 AC: 8333 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2105 AN: 3468

East Asian (EAS) AF: 0.641 AC: 3276 AN: 5112

South Asian (SAS) AF: 0.679 AC: 3276 AN: 4822

European-Finnish (FIN) AF: 0.540 AC: 5685 AN: 10526

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.637 AC: 43284 AN: 67958

Other (OTH) AF: 0.565 AC: 1189 AN: 2106

Alfa AF: 0.595 Hom.: 41592

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
PhyloP100		0.13
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: rs4659583; hg19: chr1-241039522;