dbSNP rs16900627: RIPK2:c.*351A>G (chr8-89790767-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003821.6(RIPK2):c.*351A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 193,952 control chromosomes in the GnomAD database, including 3,805 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 0.17 ( 3580 hom., cov: 32)

Exomes 𝑓: 0.081 ( 225 hom. )

Consequence

RIPK2
NM_003821.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.12

Publications

15 publications found

Variant links:

Genes affected

RIPK2 (HGNC:10020): (receptor interacting serine/threonine kinase 2) This gene encodes a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. The encoded protein contains a C-terminal caspase activation and recruitment domain (CARD), and is a component of signaling complexes in both the innate and adaptive immune pathways. It is a potent activator of NF-kappaB and inducer of apoptosis in response to various stimuli. [provided by RefSeq, Jul 2008]

RIPK2 links:

PARAIL (HGNC:55545): (palmitic acid regulated anti-inflammatory lncRNA)

PARAIL 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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RIPK2	NM_003821.6 link	c.*351A>G	3_prime_UTR_variant	Exon 11 of 11	ENST00000220751.5	NP_003812.1	O43353-1A0A0S2Z4Z8
RIPK2	NM_001375360.1 link	c.*351A>G	3_prime_UTR_variant	Exon 10 of 10		NP_001362289.1
RIPK2	XM_011517357.3 link	c.*351A>G	3_prime_UTR_variant	Exon 9 of 9		XP_011515659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPK2	ENST00000220751.5 link	c.*351A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_003821.6	ENSP00000220751.4		O43353-1

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25316

AN:

151944

Hom.:

3560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.388

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0973

Gnomad ASJ

AF:

0.106

Gnomad EAS

AF:

0.158

Gnomad SAS

AF:

0.0615

Gnomad FIN

AF:

0.0766

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.0753

Gnomad OTH

AF:

0.152

GnomAD4 exome

AF:

0.0809

AC:

3389

AN:

41890

Hom.:

225

Cov.:

AF XY:

0.0803

AC XY:

1792

AN XY:

22312

show subpopulations

African (AFR)

AF:

0.391

AC:

248

AN:

634

American (AMR)

AF:

0.0793

AC:

256

AN:

3230

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

111

AN:

908

East Asian (EAS)

AF:

0.134

AC:

287

AN:

2136

South Asian (SAS)

AF:

0.0556

AC:

285

AN:

5126

European-Finnish (FIN)

AF:

0.0789

AC:

127

AN:

1610

Middle Eastern (MID)

AF:

0.133

AC:

AN:

120

European-Non Finnish (NFE)

AF:

0.0710

AC:

1846

AN:

25994

Other (OTH)

AF:

0.0999

AC:

213

AN:

2132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

153

306

459

612

765

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.167

AC:

25373

AN:

152062

Hom.:

3580

Cov.:

AF XY:

0.163

AC XY:

12148

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.388

AC:

16088

AN:

41430

American (AMR)

AF:

0.0971

AC:

1483

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

366

AN:

3466

East Asian (EAS)

AF:

0.158

AC:

817

AN:

5180

South Asian (SAS)

AF:

0.0623

AC:

301

AN:

4828

European-Finnish (FIN)

AF:

0.0766

AC:

811

AN:

10592

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0753

AC:

5120

AN:

67972

Other (OTH)

AF:

0.151

AC:

318

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

923

1845

2768

3690

4613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

250

500

750

1000

1250

<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:

0.102

Hom.:

1632

Bravo

AF:

0.182

Asia WGS

AF:

0.110

AC:

383

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

7.9

(source)

DANN

Benign

0.75

PhyloP100

-1.1

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