1-240868599-C-T

Position:

• chr1-240868599-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.597G>A​(p.Val199=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000704 in 1,614,034 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00038 (2 hom.)
• Consequence: RGS7 NM_001364886.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.90

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=-0.72).
• BP6: Variant 1-240868599-C-T is Benign according to our data. Variant chr1-240868599-C-T is described in ClinVar as [Benign]. Clinvar id is 791845.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 575 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGS7	NM_001364886.1	c.597G>A	p.Val199=	synonymous_variant	9/19	ENST00000440928.6	NP_001351815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGS7	ENST00000440928.6	c.597G>A	p.Val199=	synonymous_variant	9/19	1	NM_001364886.1	ENSP00000404399

Frequencies

GnomAD3 genomes AF: 0.00377 AC: 573 AN: 152138 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000974 AC: 245 AN: 251462 Hom.: 2 AF XY: 0.000728 AC XY: 99 AN XY: 135910

Gnomad AFR exome AF: 0.0132

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000384 AC: 561 AN: 1461778 Hom.: 2 Cov.: 32 AF XY: 0.000305 AC XY: 222 AN XY: 727210

Gnomad4 AFR exome AF: 0.0134

Gnomad4 AMR exome AF: 0.000715

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000180

Gnomad4 OTH exome AF: 0.000894

GnomAD4 genome AF: 0.00378 AC: 575 AN: 152256 Hom.: 3 Cov.: 31 AF XY: 0.00361 AC XY: 269 AN XY: 74458

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00280 Hom.: 2

Bravo AF: 0.00471

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.13
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: rs34824344; hg19: chr1-241031899;