1-240868541-C-T

Position:

• chr1-240868541-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001364886.1(RGS7):​c.609+46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0051 in 1,570,238 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0053 (40 hom.)
• Consequence: RGS7 NM_001364886.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.344

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-240868541-C-T is Benign according to our data. Variant chr1-240868541-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3250539.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 483 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS7	NM_001364886.1	c.609+46G>A		intron_variant		ENST00000440928.6	NP_001351815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS7	ENST00000440928.6	c.609+46G>A		intron_variant		1	NM_001364886.1	ENSP00000404399

Frequencies

GnomAD3 genomes AF: 0.00318 AC: 484 AN: 152154 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.000748

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00575

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00367 AC: 921 AN: 251192 Hom.: 6 AF XY: 0.00359 AC XY: 487 AN XY: 135800

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00379

Gnomad FIN exome AF: 0.00391

Gnomad NFE exome AF: 0.00567

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00530 AC: 7520 AN: 1417966 Hom.: 40 Cov.: 27 AF XY: 0.00524 AC XY: 3711 AN XY: 708284

Gnomad4 AFR exome AF: 0.000919

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00396

Gnomad4 FIN exome AF: 0.00469

Gnomad4 NFE exome AF: 0.00603

Gnomad4 OTH exome AF: 0.00628

GnomAD4 genome AF: 0.00317 AC: 483 AN: 152272 Hom.: 4 Cov.: 31 AF XY: 0.00290 AC XY: 216 AN XY: 74456

Gnomad4 AFR AF: 0.000746

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00229

Gnomad4 FIN AF: 0.00245

Gnomad4 NFE AF: 0.00575

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00366 Hom.: 1

Bravo AF: 0.00309

Asia WGS AF: 0.00115 AC: 4 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

RGS7: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs181453607; hg19: chr1-241031841;