chr1-240800671-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001364886.1(RGS7):​c.1464G>T​(p.Leu488Leu) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L488L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RGS7 NM_001364886.1 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).

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>T	p.Leu488Leu	synonymous	Exon 18 of 19	NP_001351815.1	P49802-1
	RGS7	NM_001282775.2		c.1410G>T	p.Leu470Leu	synonymous	Exon 17 of 18	NP_001269704.1	P49802-3
	RGS7	NM_001374806.1		c.1359G>T	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>T	p.Leu488Leu	synonymous	Exon 18 of 19	ENSP00000404399.2	P49802-1
	RGS7	ENST00000348120.6	TSL:1	c.1251G>T	p.Leu417Leu	synonymous	Exon 14 of 15	ENSP00000341242.2	P49802-4
	RGS7	ENST00000366565.5	TSL:1	c.1413+784G>T		intron	N/A	ENSP00000355523.1	P49802-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	13
DANN	Benign	0.76
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;