Genetic Variant RGS16:c.221-10G>A (chr1-182602142-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002928.4(RGS16):c.221-10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 1,612,360 control chromosomes in the GnomAD database, including 118,953 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 0.33 ( 9264 hom., cov: 31)

Exomes 𝑓: 0.38 ( 109689 hom. )

Consequence

RGS16
NM_002928.4 intron

Scores

Splicing: ADA: 0.00004086

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.07

Publications

11 publications found

Variant links:

Genes affected

RGS16 (HGNC:9997): (regulator of G protein signaling 16) The protein encoded by this gene belongs to the 'regulator of G protein signaling' family. It inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits. It also may play a role in regulating the kinetics of signaling in the phototransduction cascade. [provided by RefSeq, Jul 2008]

RGS16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002928.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS16	NM_002928.4	MANE Select	c.221-10G>A		intron	N/A	NP_002919.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGS16	ENST00000367558.6	TSL:1 MANE Select	c.221-10G>A		intron	N/A	ENSP00000356529.5

Frequencies

GnomAD3 genomes

AF:

0.331

AC:

50232

AN:

151622

Hom.:

9265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.166

Gnomad AMI

AF:

0.456

Gnomad AMR

AF:

0.450

Gnomad ASJ

AF:

0.520

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.437

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.388

Gnomad OTH

AF:

0.373

GnomAD2 exomes

AF:

0.380

AC:

95368

AN:

251114

AF XY:

0.385

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.463

Gnomad ASJ exome

AF:

0.491

Gnomad EAS exome

AF:

0.237

Gnomad FIN exome

AF:

0.357

Gnomad NFE exome

AF:

0.387

Gnomad OTH exome

AF:

0.395

GnomAD4 exome

AF:

0.383

AC:

559932

AN:

1460620

Hom.:

109689

Cov.:

AF XY:

0.387

AC XY:

280851

AN XY:

726576

show subpopulations

African (AFR)

AF:

0.159

AC:

5332

AN:

33468

American (AMR)

AF:

0.468

AC:

20909

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.494

AC:

12906

AN:

26132

East Asian (EAS)

AF:

0.224

AC:

8883

AN:

39692

South Asian (SAS)

AF:

0.437

AC:

37659

AN:

86234

European-Finnish (FIN)

AF:

0.361

AC:

19266

AN:

53412

Middle Eastern (MID)

AF:

0.469

AC:

2706

AN:

5766

European-Non Finnish (NFE)

AF:

0.386

AC:

428785

AN:

1110860

Other (OTH)

AF:

0.389

AC:

23486

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

16375

32750

49125

65500

81875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13430

26860

40290

53720

67150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.331

AC:

50250

AN:

151740

Hom.:

9264

Cov.:

AF XY:

0.334

AC XY:

24730

AN XY:

74142

show subpopulations

African (AFR)

AF:

0.165

AC:

6828

AN:

41302

American (AMR)

AF:

0.451

AC:

6873

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.520

AC:

1799

AN:

3462

East Asian (EAS)

AF:

0.225

AC:

1160

AN:

5156

South Asian (SAS)

AF:

0.438

AC:

2109

AN:

4814

European-Finnish (FIN)

AF:

0.362

AC:

3803

AN:

10512

Middle Eastern (MID)

AF:

0.503

AC:

146

AN:

290

European-Non Finnish (NFE)

AF:

0.388

AC:

26325

AN:

67926

Other (OTH)

AF:

0.375

AC:

792

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1658

3316

4975

6633

8291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.351

Hom.:

3244

Bravo

AF:

0.327

Asia WGS

AF:

0.331

AC:

1152

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.082

(source)

DANN

Benign

0.36

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000041

dbscSNV1_RF

Benign

0.012

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over