rs42490

Variant names:

• chr8-89766285-G-A
• rs42490
• NM_003821.6:c.483+789G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003821.6(RIPK2):​c.483+789G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 151,632 control chromosomes in the GnomAD database, including 27,677 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain risk allele (no stars).

• Frequency: Genomes: 𝑓 0.60 (27677 hom., cov: 32)
• Consequence: RIPK2 NM_003821.6 intron
• Clinical Significance: Uncertain risk allele no assertion criteria provided O:1
• Conservation: PhyloP100: -0.275
• Publications: 41 publications found

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]

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK2	NM_003821.6	c.483+789G>A		intron_variant	Intron 3 of 10	ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1	c.72+789G>A		intron_variant	Intron 2 of 9		NP_001362289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPK2	ENST00000220751.5	c.483+789G>A		intron_variant	Intron 3 of 10	1	NM_003821.6	ENSP00000220751.4

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90629 AN: 151512 Hom.: 27640 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.592

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.598 AC: 90713 AN: 151632 Hom.: 27677 Cov.: 32 AF XY: 0.595 AC XY: 44080 AN XY: 74134

African (AFR) AF: 0.699 AC: 28936 AN: 41414

American (AMR) AF: 0.508 AC: 7720 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1488 AN: 3466

East Asian (EAS) AF: 0.462 AC: 2386 AN: 5160

South Asian (SAS) AF: 0.429 AC: 2067 AN: 4822

European-Finnish (FIN) AF: 0.632 AC: 6677 AN: 10558

Middle Eastern (MID) AF: 0.664 AC: 194 AN: 292

European-Non Finnish (NFE) AF: 0.585 AC: 39598 AN: 67700

Other (OTH) AF: 0.588 AC: 1239 AN: 2106

Alfa AF: 0.580 Hom.: 91323

Bravo AF: 0.595

Asia WGS AF: 0.460 AC: 1599 AN: 3476

ClinVar

Significance: Uncertain risk allele

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Leprosy, susceptibility to, 1 Other:1

Jun 10, 2022

Centro Dermatológico Federico Lleras Acosta, Hospital Universitario Centro Dermatológico Federico Lleras Acosta

Significance: Uncertain risk allele

Review Status: no assertion criteria provided

Collection Method: case-control

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.025
DANN	Benign	0.35
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs42490; hg19: chr8-90778513;