dbSNP rs2293168: RIC8A:c.969+133C>T (chr11-211482-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_001286134.2(RIC8A):c.969+133C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 993,170 control chromosomes in the GnomAD database, including 5,032 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 0.078 ( 1042 hom., cov: 32)

Exomes 𝑓: 0.056 ( 3990 hom. )

Consequence

RIC8A
NM_001286134.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.967

Publications

8 publications found

Variant links:

Genes affected

RIC8A (HGNC:29550): (RIC8 guanine nucleotide exchange factor A) Predicted to enable G-protein alpha-subunit binding activity; GTPase activator activity; and guanyl-nucleotide exchange factor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to act upstream of or within several processes, including basement membrane organization; gastrulation; and visual learning. Predicted to be located in membrane. Predicted to be active in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RIC8A 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIC8A	NM_001286134.2 link	c.969+133C>T		intron_variant	Intron 5 of 9	ENST00000526104.6	NP_001273063.1	Q9NPQ8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIC8A	ENST00000526104.6 link	c.969+133C>T		intron_variant	Intron 5 of 9	1	NM_001286134.2	ENSP00000432008.1		Q9NPQ8-1

Frequencies

GnomAD3 genomes

AF:

0.0777

AC:

11797

AN:

151882

Hom.:

1033

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0961

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.0283

Gnomad EAS

AF:

0.420

Gnomad SAS

AF:

0.0794

Gnomad FIN

AF:

0.0194

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0319

Gnomad OTH

AF:

0.0805

GnomAD4 exome

AF:

0.0562

AC:

47313

AN:

841170

Hom.:

3990

Cov.:

AF XY:

0.0564

AC XY:

23813

AN XY:

422520

show subpopulations

African (AFR)

AF:

0.0900

AC:

1770

AN:

19668

American (AMR)

AF:

0.210

AC:

3686

AN:

17562

Ashkenazi Jewish (ASJ)

AF:

0.0324

AC:

507

AN:

15638

East Asian (EAS)

AF:

0.404

AC:

12896

AN:

31888

South Asian (SAS)

AF:

0.0739

AC:

3806

AN:

51472

European-Finnish (FIN)

AF:

0.0212

AC:

663

AN:

31302

Middle Eastern (MID)

AF:

0.0563

AC:

153

AN:

2718

European-Non Finnish (NFE)

AF:

0.0332

AC:

21005

AN:

632470

Other (OTH)

AF:

0.0735

AC:

2827

AN:

38452

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1907

3814

5722

7629

9536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

898

1796

2694

3592

4490

<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:

0.0778

AC:

11831

AN:

152000

Hom.:

1042

Cov.:

AF XY:

0.0806

AC XY:

5990

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.0962

AC:

3987

AN:

41448

American (AMR)

AF:

0.173

AC:

2636

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.0283

AC:

AN:

3464

East Asian (EAS)

AF:

0.421

AC:

2163

AN:

5136

South Asian (SAS)

AF:

0.0792

AC:

379

AN:

4784

European-Finnish (FIN)

AF:

0.0194

AC:

206

AN:

10616

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0319

AC:

2169

AN:

67978

Other (OTH)

AF:

0.0802

AC:

169

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

489

978

1467

1956

2445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0513

Hom.:

1305

Bravo

AF:

0.0953

Asia WGS

AF:

0.214

AC:

743

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

1.2

(source)

DANN

Benign

0.60

PhyloP100

-0.97

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over