1-241036695-T-C

Variant names:

• chr1-241036695-T-C
• rs538423
• NM_001364886.1:c.176-53566A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001364886.1(RGS7):​c.176-53566A>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
• Publications: 7 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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RGS7	NM_001364886.1	c.176-53566A>G		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.176-53566A>G		intron_variant	Intron 3 of 18	1	NM_001364886.1	ENSP00000404399.2

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

African (AFR) AF: 0.0834 AC: 3464 AN: 41534

American (AMR) AF: 0.421 AC: 6439 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1748 AN: 3466

East Asian (EAS) AF: 0.685 AC: 3546 AN: 5180

South Asian (SAS) AF: 0.380 AC: 1830 AN: 4818

European-Finnish (FIN) AF: 0.435 AC: 4597 AN: 10564

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.427 AC: 29050 AN: 67978

Other (OTH) AF: 0.367 AC: 774 AN: 2108

Alfa AF: 0.388 Hom.: 27706

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
PhyloP100		-0.22
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: rs538423; hg19: chr1-241199995;