1-240868541-C-A

Variant names:

• chr1-240868541-C-A
• rs181453607
• NM_001364886.1:c.609+46G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001364886.1(RGS7):​c.609+46G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,418,020 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: RGS7 NM_001364886.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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+46G>T		intron	N/A	NP_001351815.1	P49802-1
	RGS7	NM_002924.6		c.609+46G>T		intron	N/A	NP_002915.3
	RGS7	NM_001282775.2		c.609+46G>T		intron	N/A	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.609+46G>T		intron	N/A	ENSP00000404399.2	P49802-1
	RGS7	ENST00000366565.5	TSL:1	c.609+46G>T		intron	N/A	ENSP00000355523.1	P49802-5
	RGS7	ENST00000366564.5	TSL:1	c.609+46G>T		intron	N/A	ENSP00000355522.1	P49802-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1418020 Hom.: 0 Cov.: 27 AF XY: 0.00000141 AC XY: 1 AN XY: 708306

African (AFR) AF: 0.00 AC: 0 AN: 32660

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25884

East Asian (EAS) AF: 0.00 AC: 0 AN: 39524

South Asian (SAS) AF: 0.00 AC: 0 AN: 85342

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5324

European-Non Finnish (NFE) AF: 9.32e-7 AC: 1 AN: 1072536

Other (OTH) AF: 0.00 AC: 0 AN: 58954

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.85
DANN	Benign	0.75
PhyloP100		-0.34
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: rs181453607; hg19: chr1-241031841;