Variant chr1-240827155-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001364886.1(RGS7):c.627A>G(p.Thr209=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,613,618 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0083 ( 16 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 15 hom. )

Consequence

RGS7
NM_001364886.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.874

Variant links:

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]

RGS7 links:

LOC124904602 (HGNC:):

LOC124904602 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 1-240827155-T-C is Benign according to our data. Variant chr1-240827155-T-C is described in ClinVar as [Benign]. Clinvar id is 787765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.874 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00833 (1269/152344) while in subpopulation AFR AF= 0.0274 (1140/41578). AF 95% confidence interval is 0.0261. There are 16 homozygotes in gnomad4. There are 594 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1269 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS7	NM_001364886.1 linkuse as main transcript	c.627A>G	p.Thr209=	synonymous_variant	10/19	ENST00000440928.6
LOC124904602	XR_007067053.1 linkuse as main transcript	n.155+2137T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS7	ENST00000440928.6 linkuse as main transcript	c.627A>G	p.Thr209=	synonymous_variant	10/19	1	NM_001364886.1		P49802-1

Frequencies

GnomAD3 genomes

AF:

0.00833

AC:

1268

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0275

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00484

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00241

AC:

607

AN:

251478

Hom.:

AF XY:

0.00189

AC XY:

257

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0278

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.00157

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000202

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00110

AC:

1614

AN:

1461274

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

734

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.0273

Gnomad4 AMR exome

AF:

0.00235

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.00152

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000247

Gnomad4 OTH exome

AF:

0.00265

GnomAD4 genome

AF:

0.00833

AC:

1269

AN:

152344

Hom.:

Cov.:

AF XY:

0.00797

AC XY:

594

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0274

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00464

Hom.:

Bravo

AF:

0.00992

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.6

DANN

Benign

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over