rs35467041

Variant names:

• chr1-240827155-T-C
• rs35467041
• NM_001364886.1:c.627A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001364886.1(RGS7):​c.627A>G​(p.Thr209Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,613,618 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0083 (16 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (15 hom.)
• Consequence: RGS7 NM_001364886.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.874
• Publications: 1 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

LOC124904602 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-240827155-T-C is Benign according to our data. Variant chr1-240827155-T-C is described in ClinVar as Benign. ClinVar VariationId is 787765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.874 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00833 (1269/152344) while in subpopulation AFR AF = 0.0274 (1140/41578). AF 95% confidence interval is 0.0261. There are 16 homozygotes in GnomAd4. There are 594 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 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.627A>G	p.Thr209Thr	synonymous	Exon 10 of 19	NP_001351815.1	P49802-1
	RGS7	NM_002924.6		c.627A>G	p.Thr209Thr	synonymous	Exon 10 of 18	NP_002915.3
	RGS7	NM_001282775.2		c.627A>G	p.Thr209Thr	synonymous	Exon 10 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.627A>G	p.Thr209Thr	synonymous	Exon 10 of 19	ENSP00000404399.2	P49802-1
	RGS7	ENST00000366565.5	TSL:1	c.627A>G	p.Thr209Thr	synonymous	Exon 10 of 18	ENSP00000355523.1	P49802-5
	RGS7	ENST00000366564.5	TSL:1	c.627A>G	p.Thr209Thr	synonymous	Exon 10 of 17	ENSP00000355522.1	P49802-2

Frequencies

GnomAD3 genomes AF: 0.00833 AC: 1268 AN: 152226 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00241 AC: 607 AN: 251478 AF XY: 0.00189

Gnomad AFR exome AF: 0.0278

Gnomad AMR exome AF: 0.00191

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000202

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00110 AC: 1614 AN: 1461274 Hom.: 15 Cov.: 30 AF XY: 0.00101 AC XY: 734 AN XY: 727006

African (AFR) AF: 0.0273 AC: 914 AN: 33456

American (AMR) AF: 0.00235 AC: 105 AN: 44722

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

East Asian (EAS) AF: 0.000403 AC: 16 AN: 39694

South Asian (SAS) AF: 0.00152 AC: 131 AN: 86240

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5768

European-Non Finnish (NFE) AF: 0.000247 AC: 274 AN: 1111464

Other (OTH) AF: 0.00265 AC: 160 AN: 60374

GnomAD4 genome AF: 0.00833 AC: 1269 AN: 152344 Hom.: 16 Cov.: 32 AF XY: 0.00797 AC XY: 594 AN XY: 74498

African (AFR) AF: 0.0274 AC: 1140 AN: 41578

American (AMR) AF: 0.00484 AC: 74 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68034

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00464 Hom.: 4

Bravo AF: 0.00992

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.6
DANN	Benign	0.55
PhyloP100		-0.87
Mutation Taster		=100/0	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: rs35467041; hg19: chr1-240990455;