1-240955726-T-C

Position:

• chr1-240955726-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001364886.1(RGS7):​c.227-19020A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,190 control chromosomes in the GnomAD database, including 57,769 homozygotes. 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: 𝑓 0.87 (57769 hom., cov: 31)
• Consequence: RGS7 NM_001364886.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS7	NM_001364886.1	c.227-19020A>G		intron_variant		ENST00000440928.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS7	ENST00000440928.6	c.227-19020A>G		intron_variant		1	NM_001364886.1

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132318 AN: 152072 Hom.: 57735 Cov.: 31

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.894

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.870 AC: 132403 AN: 152190 Hom.: 57769 Cov.: 31 AF XY: 0.869 AC XY: 64632 AN XY: 74382

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.930

Gnomad4 ASJ AF: 0.893

Gnomad4 EAS AF: 0.893

Gnomad4 SAS AF: 0.842

Gnomad4 FIN AF: 0.884

Gnomad4 NFE AF: 0.902

Gnomad4 OTH AF: 0.894

Alfa AF: 0.890 Hom.: 7504

Bravo AF: 0.870

Asia WGS AF: 0.863 AC: 3003 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs11805657; hg19: chr1-241119026;