chr8-100073550-G-A

Variant names:

• chr8-100073550-G-A
• rs1380994
• NM_015668.5:c.340-1320C>T

Variant summary

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

The NM_015668.5(RGS22):​c.340-1320C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,064 control chromosomes in the GnomAD database, including 11,781 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 0.38 (11781 hom., cov: 32)
• Consequence: RGS22 NM_015668.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.124
• Publications: 9 publications found

Genes affected

RGS22 (HGNC:24499): (regulator of G protein signaling 22) Enables G-protein alpha-subunit binding activity. Predicted to be involved in negative regulation of signal transduction. Located in actin cytoskeleton; cytosol; and fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

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 = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGS22	NM_015668.5	c.340-1320C>T		intron_variant	Intron 4 of 27	ENST00000360863.11	NP_056483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGS22	ENST00000360863.11	c.340-1320C>T		intron_variant	Intron 4 of 27	1	NM_015668.5	ENSP00000354109.6

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58470 AN: 151946 Hom.: 11770 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.385 AC: 58506 AN: 152064 Hom.: 11781 Cov.: 32 AF XY: 0.390 AC XY: 29009 AN XY: 74340

African (AFR) AF: 0.274 AC: 11370 AN: 41496

American (AMR) AF: 0.484 AC: 7399 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1204 AN: 3472

East Asian (EAS) AF: 0.552 AC: 2856 AN: 5170

South Asian (SAS) AF: 0.370 AC: 1784 AN: 4826

European-Finnish (FIN) AF: 0.469 AC: 4946 AN: 10546

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.408 AC: 27698 AN: 67960

Other (OTH) AF: 0.369 AC: 777 AN: 2108

Alfa AF: 0.403 Hom.: 56511

Bravo AF: 0.383

Asia WGS AF: 0.485 AC: 1687 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	1.0
DANN	Benign	0.34
PhyloP100		-0.12
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: rs1380994; hg19: chr8-101085778;