chr1-240871393-A-G

Variant names:

• chr1-240871393-A-G
• rs166370
• NM_001364886.1:c.386-1274T>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.386-1274T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,988 control chromosomes in the GnomAD database, including 14,739 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 0.41 (14739 hom., cov: 32)
• Consequence: RGS7 NM_001364886.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.66 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.386-1274T>C		intron	N/A	NP_001351815.1
	RGS7	NM_002924.6		c.386-1274T>C		intron	N/A	NP_002915.3
	RGS7	NM_001282775.2		c.386-1274T>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.386-1274T>C		intron	N/A	ENSP00000404399.2
	RGS7	ENST00000366565.5	TSL:1	c.386-1274T>C		intron	N/A	ENSP00000355523.1
	RGS7	ENST00000366564.5	TSL:1	c.386-1274T>C		intron	N/A	ENSP00000355522.1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61507 AN: 151870 Hom.: 14699 Cov.: 32

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.458

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.405 AC: 61592 AN: 151988 Hom.: 14739 Cov.: 32 AF XY: 0.398 AC XY: 29601 AN XY: 74298

African (AFR) AF: 0.667 AC: 27623 AN: 41424

American (AMR) AF: 0.254 AC: 3880 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1476 AN: 3470

East Asian (EAS) AF: 0.177 AC: 912 AN: 5152

South Asian (SAS) AF: 0.306 AC: 1475 AN: 4818

European-Finnish (FIN) AF: 0.307 AC: 3242 AN: 10570

Middle Eastern (MID) AF: 0.441 AC: 128 AN: 290

European-Non Finnish (NFE) AF: 0.319 AC: 21687 AN: 67966

Other (OTH) AF: 0.379 AC: 803 AN: 2116

Alfa AF: 0.342 Hom.: 41278

Bravo AF: 0.413

Asia WGS AF: 0.257 AC: 893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.5
DANN	Benign	0.57
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs166370; hg19: chr1-241034693;