1-240776091-C-T

Variant names:

• chr1-240776091-C-T
• rs12757054
• NM_001364886.1:c.*129G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001364886.1(RGS7):​c.*129G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 1,150,318 control chromosomes in the GnomAD database, including 3,479 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 0.061 (354 hom., cov: 32)
  • Exomes 𝑓: 0.074 (3125 hom.)
• Consequence: RGS7 NM_001364886.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• Publications: 9 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

ENSG00000226919 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS7	NM_001364886.1	c.*129G>A		3_prime_UTR_variant	Exon 19 of 19	ENST00000440928.6	NP_001351815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS7	ENST00000440928.6	c.*129G>A		3_prime_UTR_variant	Exon 19 of 19	1	NM_001364886.1	ENSP00000404399.2

Frequencies

GnomAD3 genomes AF: 0.0610 AC: 9276 AN: 152090 Hom.: 353 Cov.: 32

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0458

Gnomad ASJ AF: 0.0868

Gnomad EAS AF: 0.0241

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.0324

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0823

Gnomad OTH AF: 0.0602

GnomAD4 exome AF: 0.0742 AC: 74071 AN: 998110 Hom.: 3125 Cov.: 13 AF XY: 0.0754 AC XY: 39049 AN XY: 517592

African (AFR) AF: 0.0371 AC: 904 AN: 24384

American (AMR) AF: 0.0389 AC: 1716 AN: 44112

Ashkenazi Jewish (ASJ) AF: 0.0855 AC: 1990 AN: 23286

East Asian (EAS) AF: 0.0165 AC: 620 AN: 37568

South Asian (SAS) AF: 0.0920 AC: 7069 AN: 76836

European-Finnish (FIN) AF: 0.0351 AC: 1868 AN: 53154

Middle Eastern (MID) AF: 0.0901 AC: 442 AN: 4906

European-Non Finnish (NFE) AF: 0.0818 AC: 56297 AN: 688582

Other (OTH) AF: 0.0699 AC: 3165 AN: 45282

GnomAD4 genome AF: 0.0610 AC: 9279 AN: 152208 Hom.: 354 Cov.: 32 AF XY: 0.0596 AC XY: 4435 AN XY: 74440

African (AFR) AF: 0.0390 AC: 1621 AN: 41524

American (AMR) AF: 0.0458 AC: 700 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0868 AC: 301 AN: 3468

East Asian (EAS) AF: 0.0244 AC: 126 AN: 5166

South Asian (SAS) AF: 0.0839 AC: 405 AN: 4830

European-Finnish (FIN) AF: 0.0324 AC: 343 AN: 10602

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0823 AC: 5595 AN: 68006

Other (OTH) AF: 0.0610 AC: 129 AN: 2114

Alfa AF: 0.0757 Hom.: 611

Bravo AF: 0.0599

Asia WGS AF: 0.0620 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.65
PhyloP100		1.6
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: rs12757054; hg19: chr1-240939391; COSMIC: COSV58544216; COSMIC: COSV58544216;