1-240998475-C-T

Position:

• chr1-240998475-C-T

Variant summary

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

The NM_001364886.1(RGS7):​c.176-15346G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 988,622 control chromosomes in the GnomAD database, including 53,551 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 0.32 (8032 hom., cov: 31)
  • Exomes 𝑓: 0.32 (45519 hom.)
• Consequence: RGS7 NM_001364886.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS7	NM_001364886.1	c.176-15346G>A		intron_variant		ENST00000440928.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS7	ENST00000440928.6	c.176-15346G>A		intron_variant		1	NM_001364886.1
	ENST00000437248.1	n.320G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47984 AN: 151776 Hom.: 8029 Cov.: 31

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.356

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.319 AC: 266610 AN: 836726 Hom.: 45519 Cov.: 12 AF XY: 0.322 AC XY: 141601 AN XY: 439550

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.532

Gnomad4 ASJ exome AF: 0.338

Gnomad4 EAS exome AF: 0.305

Gnomad4 SAS exome AF: 0.365

Gnomad4 FIN exome AF: 0.331

Gnomad4 NFE exome AF: 0.302

Gnomad4 OTH exome AF: 0.322

GnomAD4 genome AF: 0.316 AC: 48000 AN: 151896 Hom.: 8032 Cov.: 31 AF XY: 0.319 AC XY: 23714 AN XY: 74226

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.340

Alfa AF: 0.195 Hom.: 488

Bravo AF: 0.320

Asia WGS AF: 0.303 AC: 1053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.3
DANN	Benign	0.79

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: rs670659; hg19: chr1-241161775; COSMIC: COSV58539342;