1-241036695-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.176-53566A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,136 control chromosomes in the GnomAD database, including 11,076 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 0.34 (11076 hom., cov: 33)
• Consequence: RGS7 NM_001364886.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS7	NM_001364886.1	c.176-53566A>G		intron_variant		ENST00000440928.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS7	ENST00000440928.6	c.176-53566A>G		intron_variant		1	NM_001364886.1

Frequencies

GnomAD3 genomes AF: 0.342 AC: 52024 AN: 152018 Hom.: 11075 Cov.: 33

Gnomad AFR AF: 0.0837

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.342 AC: 52015 AN: 152136 Hom.: 11076 Cov.: 33 AF XY: 0.347 AC XY: 25837 AN XY: 74376

Gnomad4 AFR AF: 0.0834

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.367

Alfa AF: 0.414 Hom.: 19621

Bravo AF: 0.329

Asia WGS AF: 0.501 AC: 1740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.4
Dann	Benign	0.63

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: rs538423; hg19: chr1-241199995;