rs716743

Variant names:

• chr1-240849479-T-A
• rs716743
• NM_001364886.1:c.609+19108A>T

Variant summary

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

The NM_001364886.1(RGS7):​c.609+19108A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 152,192 control chromosomes in the GnomAD database, including 49,638 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 0.80 (49638 hom., cov: 32)
• Consequence: RGS7 NM_001364886.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.894 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.609+19108A>T		intron	N/A	NP_001351815.1
	RGS7	NM_002924.6		c.609+19108A>T		intron	N/A	NP_002915.3
	RGS7	NM_001282775.2		c.609+19108A>T		intron	N/A	NP_001269704.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS7	ENST00000440928.6	TSL:1 MANE Select	c.609+19108A>T		intron	N/A	ENSP00000404399.2
	RGS7	ENST00000366565.5	TSL:1	c.609+19108A>T		intron	N/A	ENSP00000355523.1
	RGS7	ENST00000366564.5	TSL:1	c.609+19108A>T		intron	N/A	ENSP00000355522.1

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122283 AN: 152072 Hom.: 49598 Cov.: 32

Gnomad AFR AF: 0.902

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.804 AC: 122376 AN: 152192 Hom.: 49638 Cov.: 32 AF XY: 0.798 AC XY: 59327 AN XY: 74386

African (AFR) AF: 0.902 AC: 37488 AN: 41558

American (AMR) AF: 0.749 AC: 11447 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2746 AN: 3468

East Asian (EAS) AF: 0.604 AC: 3124 AN: 5174

South Asian (SAS) AF: 0.693 AC: 3334 AN: 4814

European-Finnish (FIN) AF: 0.727 AC: 7689 AN: 10574

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.795 AC: 54038 AN: 68008

Other (OTH) AF: 0.776 AC: 1639 AN: 2112

Alfa AF: 0.804 Hom.: 6161

Bravo AF: 0.811

Asia WGS AF: 0.650 AC: 2267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.80
PhyloP100		1.1
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: rs716743; hg19: chr1-241012779;