1-240882312-G-T

Variant names:

• chr1-240882312-G-T
• rs377116
• NM_001364886.1:c.386-12193C>A

Variant summary

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

The NM_001364886.1(RGS7):​c.386-12193C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 151,904 control chromosomes in the GnomAD database, including 16,901 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 0.47 (16901 hom., cov: 32)
• Consequence: RGS7 NM_001364886.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441
• Publications: 1 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS7	NM_001364886.1	c.386-12193C>A		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.386-12193C>A		intron_variant	Intron 6 of 18	1	NM_001364886.1	ENSP00000404399.2

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71129 AN: 151786 Hom.: 16889 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.469 AC: 71171 AN: 151904 Hom.: 16901 Cov.: 32 AF XY: 0.468 AC XY: 34743 AN XY: 74246

African (AFR) AF: 0.386 AC: 15994 AN: 41420

American (AMR) AF: 0.478 AC: 7299 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1447 AN: 3466

East Asian (EAS) AF: 0.534 AC: 2757 AN: 5160

South Asian (SAS) AF: 0.517 AC: 2493 AN: 4820

European-Finnish (FIN) AF: 0.443 AC: 4674 AN: 10552

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34926 AN: 67904

Other (OTH) AF: 0.454 AC: 958 AN: 2110

Alfa AF: 0.426 Hom.: 2360

Bravo AF: 0.463

Asia WGS AF: 0.505 AC: 1761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.32
DANN	Benign	0.73
PhyloP100		-0.44
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: rs377116; hg19: chr1-241045612;