1-240998475-C-T

Variant names:

• chr1-240998475-C-T
• rs670659
• NM_001364886.1:c.176-15346G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ENSG00000238085 (HGNC:):

RPLP1P2 (HGNC:36210):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RGS7	NM_001364886.1	c.176-15346G>A		intron_variant	Intron 3 of 18	ENST00000440928.6	NP_001351815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS7	ENST00000440928.6	c.176-15346G>A		intron_variant	Intron 3 of 18	1	NM_001364886.1	ENSP00000404399.2

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

African (AFR) AF: 0.180 AC: 3820 AN: 21280

American (AMR) AF: 0.532 AC: 20675 AN: 38868

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 6895 AN: 20422

East Asian (EAS) AF: 0.305 AC: 10685 AN: 35038

South Asian (SAS) AF: 0.365 AC: 26506 AN: 72706

European-Finnish (FIN) AF: 0.331 AC: 11443 AN: 34572

Middle Eastern (MID) AF: 0.382 AC: 1037 AN: 2716

European-Non Finnish (NFE) AF: 0.302 AC: 173173 AN: 572666

Other (OTH) AF: 0.322 AC: 12376 AN: 38458

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

African (AFR) AF: 0.205 AC: 8483 AN: 41430

American (AMR) AF: 0.457 AC: 6975 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1203 AN: 3464

East Asian (EAS) AF: 0.320 AC: 1648 AN: 5156

South Asian (SAS) AF: 0.348 AC: 1674 AN: 4810

European-Finnish (FIN) AF: 0.331 AC: 3481 AN: 10514

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.346 AC: 23510 AN: 67950

Other (OTH) AF: 0.340 AC: 718 AN: 2112

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
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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