rs16900627

Positions:

• chr8-89790767-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPK2	NM_003821.6	c.*351A>G		3_prime_UTR_variant	11/11	ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1	c.*351A>G		3_prime_UTR_variant	10/10		NP_001362289.1
RIPK2	XM_011517357.3	c.*351A>G		3_prime_UTR_variant	9/9		XP_011515659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPK2	ENST00000220751.5	c.*351A>G		3_prime_UTR_variant	11/11	1	NM_003821.6	ENSP00000220751.4

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25316 AN: 151944 Hom.: 3560 Cov.: 32

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.: 0 AF XY: 0.0803 AC XY: 1792 AN XY: 22312

Gnomad4 AFR exome AF: 0.391

Gnomad4 AMR exome AF: 0.0793

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.134

Gnomad4 SAS exome AF: 0.0556

Gnomad4 FIN exome AF: 0.0789

Gnomad4 NFE exome AF: 0.0710

Gnomad4 OTH exome AF: 0.0999

GnomAD4 genome AF: 0.167 AC: 25373 AN: 152062 Hom.: 3580 Cov.: 32 AF XY: 0.163 AC XY: 12148 AN XY: 74356

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.0971

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.0623

Gnomad4 FIN AF: 0.0766

Gnomad4 NFE AF: 0.0753

Gnomad4 OTH AF: 0.151

Alfa AF: 0.101 Hom.: 1250

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
DANN	Benign	0.75

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

LitVar

Other links and lift over

dbSNP: rs16900627; hg19: chr8-90802995;