8-89767579-A-G

Variant names:

• chr8-89767579-A-G
• rs39503
• NM_003821.6:c.483+2083A>G

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+2083A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,506 control chromosomes in the GnomAD database, including 34,594 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 0.66 (34594 hom., cov: 31)
• Consequence: RIPK2 NM_003821.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350
• Publications: 7 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003821.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK2	NM_003821.6	MANE Select	c.483+2083A>G		intron	N/A	NP_003812.1
	RIPK2	NM_001375360.1		c.72+2083A>G		intron	N/A	NP_001362289.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK2	ENST00000220751.5	TSL:1 MANE Select	c.483+2083A>G		intron	N/A	ENSP00000220751.4
	RIPK2	ENST00000522965.1	TSL:1	n.*122+2083A>G		intron	N/A	ENSP00000429271.1
	PARAIL	ENST00000814457.1		n.650-41938T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99567 AN: 151388 Hom.: 34541 Cov.: 31

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.658 AC: 99676 AN: 151506 Hom.: 34594 Cov.: 31 AF XY: 0.653 AC XY: 48348 AN XY: 74034

African (AFR) AF: 0.891 AC: 36946 AN: 41464

American (AMR) AF: 0.533 AC: 8097 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1512 AN: 3460

East Asian (EAS) AF: 0.529 AC: 2730 AN: 5156

South Asian (SAS) AF: 0.445 AC: 2147 AN: 4826

European-Finnish (FIN) AF: 0.632 AC: 6670 AN: 10556

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.587 AC: 39625 AN: 67558

Other (OTH) AF: 0.637 AC: 1338 AN: 2102

Alfa AF: 0.590 Hom.: 13825

Bravo AF: 0.663

Asia WGS AF: 0.519 AC: 1803 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.70
PhyloP100		-0.35
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: rs39503; hg19: chr8-90779807;