8-89773457-C-T

Variant names:

• chr8-89773457-C-T
• rs447618
• NM_003821.6:c.853+629C>T

Variant summary

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

The NM_003821.6(RIPK2):​c.853+629C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 152,008 control chromosomes in the GnomAD database, including 34,904 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 (34904 hom., cov: 32)
• Consequence: RIPK2 NM_003821.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 8 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 = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK2	NM_003821.6	c.853+629C>T		intron_variant	Intron 6 of 10	ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1	c.442+629C>T		intron_variant	Intron 5 of 9		NP_001362289.1
RIPK2	XM_011517357.3	c.340+629C>T		intron_variant	Intron 4 of 8		XP_011515659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPK2	ENST00000220751.5	c.853+629C>T		intron_variant	Intron 6 of 10	1	NM_003821.6	ENSP00000220751.4

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100150 AN: 151890 Hom.: 34851 Cov.: 32

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.692

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.660 AC: 100258 AN: 152008 Hom.: 34904 Cov.: 32 AF XY: 0.655 AC XY: 48629 AN XY: 74278

African (AFR) AF: 0.897 AC: 37225 AN: 41506

American (AMR) AF: 0.534 AC: 8151 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1514 AN: 3462

East Asian (EAS) AF: 0.529 AC: 2736 AN: 5168

South Asian (SAS) AF: 0.445 AC: 2147 AN: 4820

European-Finnish (FIN) AF: 0.633 AC: 6676 AN: 10548

Middle Eastern (MID) AF: 0.690 AC: 200 AN: 290

European-Non Finnish (NFE) AF: 0.587 AC: 39857 AN: 67922

Other (OTH) AF: 0.637 AC: 1344 AN: 2110

Alfa AF: 0.588 Hom.: 13549

Bravo AF: 0.664

Asia WGS AF: 0.521 AC: 1809 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.059
DANN	Benign	0.17
PhyloP100		-1.1
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: rs447618; hg19: chr8-90785685;