1-240800671-C-T

Variant names:

• chr1-240800671-C-T
• rs199591879
• NM_001364886.1:c.1464G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4 BP6_Moderate

The NM_001364886.1(RGS7):​c.1464G>A​(p.Leu488Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.000255 in 1,547,766 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00025 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (1 hom.)
• Consequence: RGS7 NM_001364886.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.37
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).
• BP6: Variant 1-240800671-C-T is Benign according to our data. Variant chr1-240800671-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3025043.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1464G>A	p.Leu488Leu	synonymous	Exon 18 of 19	NP_001351815.1	P49802-1
	RGS7	NM_001282775.2		c.1410G>A	p.Leu470Leu	synonymous	Exon 17 of 18	NP_001269704.1	P49802-3
	RGS7	NM_001374806.1		c.1359G>A	p.Leu453Leu	synonymous	Exon 16 of 17	NP_001361735.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS7	ENST00000440928.6	TSL:1 MANE Select	c.1464G>A	p.Leu488Leu	synonymous	Exon 18 of 19	ENSP00000404399.2	P49802-1
	RGS7	ENST00000348120.6	TSL:1	c.1251G>A	p.Leu417Leu	synonymous	Exon 14 of 15	ENSP00000341242.2	P49802-4
	RGS7	ENST00000366565.5	TSL:1	c.1413+784G>A		intron	N/A	ENSP00000355523.1	P49802-5

Frequencies

GnomAD3 genomes AF: 0.000250 AC: 38 AN: 152086 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000374 AC: 56 AN: 149920 AF XY: 0.000411

Gnomad AFR exome AF: 0.000142

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00381

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000376

Gnomad OTH exome AF: 0.000459

GnomAD4 exome AF: 0.000255 AC: 356 AN: 1395680 Hom.: 1 Cov.: 28 AF XY: 0.000283 AC XY: 195 AN XY: 688420

African (AFR) AF: 0.0000318 AC: 1 AN: 31464

American (AMR) AF: 0.00 AC: 0 AN: 35600

Ashkenazi Jewish (ASJ) AF: 0.00395 AC: 99 AN: 25068

East Asian (EAS) AF: 0.00 AC: 0 AN: 35654

South Asian (SAS) AF: 0.00 AC: 0 AN: 79046

European-Finnish (FIN) AF: 0.0000414 AC: 2 AN: 48284

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5686

European-Non Finnish (NFE) AF: 0.000218 AC: 235 AN: 1076940

Other (OTH) AF: 0.000311 AC: 18 AN: 57938

GnomAD4 genome AF: 0.000250 AC: 38 AN: 152086 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74274

African (AFR) AF: 0.0000241 AC: 1 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00577 AC: 20 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000506 Hom.: 1

Bravo AF: 0.000185

ClinVar

ClinVar submissions

Significance: Likely 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	-0.18
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		5.4
Mutation Taster		=99/1	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: rs199591879; hg19: chr1-240963971;