1-240955726-T-C

Variant names:

• chr1-240955726-T-C
• rs11805657
• NM_001364886.1:c.227-19020A>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.227-19020A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,190 control chromosomes in the GnomAD database, including 57,769 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 0.87 (57769 hom., cov: 31)
• Consequence: RGS7 NM_001364886.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364886.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS7	NM_001364886.1	MANE Select	c.227-19020A>G		intron	N/A	NP_001351815.1	P49802-1
	RGS7	NM_002924.6		c.227-19020A>G		intron	N/A	NP_002915.3
	RGS7	NM_001282775.2		c.227-19020A>G		intron	N/A	NP_001269704.1	P49802-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS7	ENST00000440928.6	TSL:1 MANE Select	c.227-19020A>G		intron	N/A	ENSP00000404399.2	P49802-1
	RGS7	ENST00000366565.5	TSL:1	c.227-19020A>G		intron	N/A	ENSP00000355523.1	P49802-5
	RGS7	ENST00000366564.5	TSL:1	c.227-19020A>G		intron	N/A	ENSP00000355522.1	P49802-2

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132318 AN: 152072 Hom.: 57735 Cov.: 31

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.894

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

GnomAD4 genome AF: 0.870 AC: 132403 AN: 152190 Hom.: 57769 Cov.: 31 AF XY: 0.869 AC XY: 64632 AN XY: 74382

African (AFR) AF: 0.789 AC: 32743 AN: 41496

American (AMR) AF: 0.930 AC: 14220 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.893 AC: 3099 AN: 3472

East Asian (EAS) AF: 0.893 AC: 4621 AN: 5174

South Asian (SAS) AF: 0.842 AC: 4062 AN: 4826

European-Finnish (FIN) AF: 0.884 AC: 9360 AN: 10588

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.902 AC: 61366 AN: 68024

Other (OTH) AF: 0.894 AC: 1889 AN: 2112

Alfa AF: 0.890 Hom.: 7504

Bravo AF: 0.870

Asia WGS AF: 0.863 AC: 3003 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.72
PhyloP100		-0.28
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: rs11805657; hg19: chr1-241119026;