1-241354678-T-C

Variant names:

• chr1-241354678-T-C
• rs1341467
• NM_001364886.1:c.78+1021A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001350113.2(RGS7):​c.-102A>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,096 control chromosomes in the GnomAD database, including 31,469 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 0.63 (31469 hom., cov: 33)
• Consequence: RGS7 NM_001350113.2 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350113.2. 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.78+1021A>G		intron	N/A	NP_001351815.1	P49802-1
	RGS7	NM_001350113.2		c.-102A>G		splice_region	Exon 3 of 19	NP_001337042.1	B7Z257
	RGS7	NM_001350115.2		c.-102A>G		splice_region	Exon 3 of 18	NP_001337044.1	A0A8I5KXW5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS7	ENST00000440928.6	TSL:1 MANE Select	c.78+1021A>G		intron	N/A	ENSP00000404399.2	P49802-1
	RGS7	ENST00000366565.5	TSL:1	c.78+1021A>G		intron	N/A	ENSP00000355523.1	P49802-5
	RGS7	ENST00000366564.5	TSL:1	c.78+1021A>G		intron	N/A	ENSP00000355522.1	P49802-2

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95475 AN: 151976 Hom.: 31456 Cov.: 33

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.628 AC: 95513 AN: 152096 Hom.: 31469 Cov.: 33 AF XY: 0.629 AC XY: 46797 AN XY: 74360

African (AFR) AF: 0.410 AC: 16991 AN: 41474

American (AMR) AF: 0.643 AC: 9828 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2554 AN: 3466

East Asian (EAS) AF: 0.763 AC: 3952 AN: 5178

South Asian (SAS) AF: 0.645 AC: 3110 AN: 4818

European-Finnish (FIN) AF: 0.715 AC: 7559 AN: 10570

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.728 AC: 49527 AN: 67990

Other (OTH) AF: 0.639 AC: 1349 AN: 2112

Alfa AF: 0.705 Hom.: 22346

Bravo AF: 0.610

Asia WGS AF: 0.663 AC: 2307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	17
DANN	Benign	0.78
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1341467; hg19: chr1-241517978;