NM_001364886.1:c.78+22792T>G

Variant names:

• chr1-241332907-A-C
• rs876437
• NM_001364886.1:c.78+22792T>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.78+22792T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,100 control chromosomes in the GnomAD database, including 7,044 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 0.28 (7044 hom., cov: 32)
• Consequence: RGS7 NM_001364886.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS7	NM_001364886.1	c.78+22792T>G		intron_variant	Intron 2 of 18	ENST00000440928.6	NP_001351815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS7	ENST00000440928.6	c.78+22792T>G		intron_variant	Intron 2 of 18	1	NM_001364886.1	ENSP00000404399.2

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43142 AN: 151982 Hom.: 7024 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.284 AC: 43200 AN: 152100 Hom.: 7044 Cov.: 32 AF XY: 0.282 AC XY: 20969 AN XY: 74378

African (AFR) AF: 0.443 AC: 18367 AN: 41458

American (AMR) AF: 0.188 AC: 2865 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1141 AN: 3468

East Asian (EAS) AF: 0.299 AC: 1545 AN: 5170

South Asian (SAS) AF: 0.266 AC: 1281 AN: 4824

European-Finnish (FIN) AF: 0.220 AC: 2332 AN: 10592

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14730 AN: 67994

Other (OTH) AF: 0.265 AC: 560 AN: 2112

Alfa AF: 0.306 Hom.: 3524

Bravo AF: 0.288

Asia WGS AF: 0.271 AC: 941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.60
DANN	Benign	0.80
PhyloP100		-1.3
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: rs876437; hg19: chr1-241496207;