rs34824344

Variant names:

• chr1-240868599-C-T
• rs34824344
• NM_001364886.1:c.597G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-240868599-C-T
• chr1-240868599-C-A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001364886.1(RGS7):​c.597G>A​(p.Val199Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000704 in 1,614,034 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00038 (2 hom.)
• Consequence: RGS7 NM_001364886.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.90
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 1-240868599-C-T is Benign according to our data. Variant chr1-240868599-C-T is described in ClinVar as Benign. ClinVar VariationId is 791845.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.597G>A	p.Val199Val	synonymous	Exon 9 of 19	NP_001351815.1	P49802-1
	RGS7	NM_002924.6		c.597G>A	p.Val199Val	synonymous	Exon 9 of 18	NP_002915.3
	RGS7	NM_001282775.2		c.597G>A	p.Val199Val	synonymous	Exon 9 of 18	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.597G>A	p.Val199Val	synonymous	Exon 9 of 19	ENSP00000404399.2	P49802-1
	RGS7	ENST00000366565.5	TSL:1	c.597G>A	p.Val199Val	synonymous	Exon 9 of 18	ENSP00000355523.1	P49802-5
	RGS7	ENST00000366564.5	TSL:1	c.597G>A	p.Val199Val	synonymous	Exon 9 of 17	ENSP00000355522.1	P49802-2

Frequencies

GnomAD3 genomes AF: 0.00377 AC: 573 AN: 152138 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000974 AC: 245 AN: 251462 AF XY: 0.000728

Gnomad AFR exome AF: 0.0132

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000384 AC: 561 AN: 1461778 Hom.: 2 Cov.: 32 AF XY: 0.000305 AC XY: 222 AN XY: 727210

African (AFR) AF: 0.0134 AC: 449 AN: 33470

American (AMR) AF: 0.000715 AC: 32 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.0000180 AC: 20 AN: 1111924

Other (OTH) AF: 0.000894 AC: 54 AN: 60390

GnomAD4 genome AF: 0.00378 AC: 575 AN: 152256 Hom.: 3 Cov.: 31 AF XY: 0.00361 AC XY: 269 AN XY: 74458

African (AFR) AF: 0.0133 AC: 551 AN: 41534

American (AMR) AF: 0.00118 AC: 18 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68014

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00253 Hom.: 2

Bravo AF: 0.00471

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.13
DANN	Benign	0.72
PhyloP100		-1.9
Mutation Taster		=98/2	polymorphism

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: rs34824344; hg19: chr1-241031899;