chr1-240891165-A-G

Variant names:

• chr1-240891165-A-G
• rs261809
• NM_001364886.1:c.386-21046T>C

Variant summary

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

The NM_001364886.1(RGS7):​c.386-21046T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 151,956 control chromosomes in the GnomAD database, including 25,311 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 0.57 (25311 hom., cov: 31)
• Consequence: RGS7 NM_001364886.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS7	NM_001364886.1	MANE Select	c.386-21046T>C		intron	N/A	NP_001351815.1
	RGS7	NM_002924.6		c.386-21046T>C		intron	N/A	NP_002915.3
	RGS7	NM_001282775.2		c.386-21046T>C		intron	N/A	NP_001269704.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS7	ENST00000440928.6	TSL:1 MANE Select	c.386-21046T>C		intron	N/A	ENSP00000404399.2
	RGS7	ENST00000366565.5	TSL:1	c.386-21046T>C		intron	N/A	ENSP00000355523.1
	RGS7	ENST00000366564.5	TSL:1	c.386-21046T>C		intron	N/A	ENSP00000355522.1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86654 AN: 151838 Hom.: 25278 Cov.: 31

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.571 AC: 86739 AN: 151956 Hom.: 25311 Cov.: 31 AF XY: 0.568 AC XY: 42204 AN XY: 74278

African (AFR) AF: 0.699 AC: 28965 AN: 41436

American (AMR) AF: 0.535 AC: 8166 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1424 AN: 3468

East Asian (EAS) AF: 0.540 AC: 2791 AN: 5170

South Asian (SAS) AF: 0.555 AC: 2677 AN: 4820

European-Finnish (FIN) AF: 0.458 AC: 4833 AN: 10550

Middle Eastern (MID) AF: 0.541 AC: 157 AN: 290

European-Non Finnish (NFE) AF: 0.532 AC: 36176 AN: 67946

Other (OTH) AF: 0.527 AC: 1109 AN: 2104

Alfa AF: 0.574 Hom.: 8620

Bravo AF: 0.577

Asia WGS AF: 0.572 AC: 1991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.8
DANN	Benign	0.80
PhyloP100		-0.032
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: rs261809; hg19: chr1-241054465;