dbSNP rs11246002: RIC8A:c.969+98G>A (chr11-211447-G-A) – 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+98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0474 in 1,298,186 control chromosomes in the GnomAD database, including 1,917 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 0.049 ( 232 hom., cov: 32)

Exomes 𝑓: 0.047 ( 1685 hom. )

Consequence

RIC8A
NM_001286134.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0280

Publications

7 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIC8A	NM_001286134.2 link	c.969+98G>A		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+98G>A		intron_variant	Intron 5 of 9	1	NM_001286134.2	ENSP00000432008.1		Q9NPQ8-1

Frequencies

GnomAD3 genomes

AF:

0.0492

AC:

7479

AN:

151964

Hom.:

233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0616

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0459

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.0988

Gnomad FIN

AF:

0.0232

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0381

Gnomad OTH

AF:

0.0416

GnomAD4 exome

AF:

0.0471

AC:

54004

AN:

1146104

Hom.:

1685

Cov.:

AF XY:

0.0484

AC XY:

27541

AN XY:

569106

show subpopulations

African (AFR)

AF:

0.0648

AC:

1680

AN:

25930

American (AMR)

AF:

0.0338

AC:

898

AN:

26598

Ashkenazi Jewish (ASJ)

AF:

0.0212

AC:

389

AN:

18376

East Asian (EAS)

AF:

0.124

AC:

4459

AN:

35852

South Asian (SAS)

AF:

0.0975

AC:

6127

AN:

62856

European-Finnish (FIN)

AF:

0.0218

AC:

807

AN:

36952

Middle Eastern (MID)

AF:

0.0531

AC:

196

AN:

3688

European-Non Finnish (NFE)

AF:

0.0417

AC:

37027

AN:

887164

Other (OTH)

AF:

0.0497

AC:

2421

AN:

48688

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

2436

4871

7307

9742

12178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1536

3072

4608

6144

7680

<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:

0.0492

AC:

7475

AN:

152082

Hom.:

232

Cov.:

AF XY:

0.0496

AC XY:

3684

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.0614

AC:

2548

AN:

41466

American (AMR)

AF:

0.0458

AC:

700

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

AN:

3470

East Asian (EAS)

AF:

0.143

AC:

736

AN:

5164

South Asian (SAS)

AF:

0.0987

AC:

473

AN:

4794

European-Finnish (FIN)

AF:

0.0232

AC:

246

AN:

10606

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0381

AC:

2592

AN:

67984

Other (OTH)

AF:

0.0421

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

343

686

1028

1371

1714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.0426

Hom.:

Bravo

AF:

0.0513

Asia WGS

AF:

0.117

AC:

405

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.4

(source)

DANN

Benign

0.78

PhyloP100

-0.028

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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