chr1-241001226-T-C

Position:

• chr1-241001226-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.176-18097A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,044 control chromosomes in the GnomAD database, including 10,408 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 0.35 (10408 hom., cov: 31)
• Consequence: RGS7 NM_001364886.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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 (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS7	NM_001364886.1	c.176-18097A>G		intron_variant		ENST00000440928.6	NP_001351815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS7	ENST00000440928.6	c.176-18097A>G		intron_variant		1	NM_001364886.1	ENSP00000404399

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53625 AN: 151926 Hom.: 10402 Cov.: 31

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.353

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

GnomAD4 genome AF: 0.353 AC: 53649 AN: 152044 Hom.: 10408 Cov.: 31 AF XY: 0.354 AC XY: 26305 AN XY: 74308

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.356

Alfa AF: 0.401 Hom.: 17006

Bravo AF: 0.338

Asia WGS AF: 0.535 AC: 1858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.5
DANN	Benign	0.56

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: rs2502448; hg19: chr1-241164526;