NM_003821.6:c.1470A>G

Variant names:

• chr8-89790263-A-G
• rs16900617
• NM_003821.6:c.1470A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003821.6(RIPK2):​c.1470A>G​(p.Leu490Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,614,028 control chromosomes in the GnomAD database, including 1,553 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 0.058 (778 hom., cov: 32)
  • Exomes 𝑓: 0.0083 (775 hom.)
• Consequence: RIPK2 NM_003821.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 11 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=-0.096 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 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.1470A>G	p.Leu490Leu	synonymous	Exon 11 of 11	NP_003812.1
	RIPK2	NM_001375360.1		c.1059A>G	p.Leu353Leu	synonymous	Exon 10 of 10	NP_001362289.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK2	ENST00000220751.5	TSL:1 MANE Select	c.1470A>G	p.Leu490Leu	synonymous	Exon 11 of 11	ENSP00000220751.4
	RIPK2	ENST00000522965.1	TSL:1	n.*1109A>G		non_coding_transcript_exon	Exon 10 of 10	ENSP00000429271.1
	RIPK2	ENST00000522965.1	TSL:1	n.*1109A>G		3_prime_UTR	Exon 10 of 10	ENSP00000429271.1

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8769 AN: 152080 Hom.: 771 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0253

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.0673

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00154

Gnomad OTH AF: 0.0464

GnomAD2 exomes AF: 0.0208 AC: 5232 AN: 251104 AF XY: 0.0166

Gnomad AFR exome AF: 0.196

Gnomad AMR exome AF: 0.0112

Gnomad ASJ exome AF: 0.00655

Gnomad EAS exome AF: 0.0608

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00119

Gnomad OTH exome AF: 0.0118

GnomAD4 exome AF: 0.00827 AC: 12088 AN: 1461830 Hom.: 775 Cov.: 31 AF XY: 0.00782 AC XY: 5686 AN XY: 727228

African (AFR) AF: 0.194 AC: 6487 AN: 33474

American (AMR) AF: 0.0118 AC: 529 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00719 AC: 188 AN: 26134

East Asian (EAS) AF: 0.0510 AC: 2025 AN: 39692

South Asian (SAS) AF: 0.00953 AC: 822 AN: 86258

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53416

Middle Eastern (MID) AF: 0.0158 AC: 91 AN: 5768

European-Non Finnish (NFE) AF: 0.000690 AC: 767 AN: 1111974

Other (OTH) AF: 0.0195 AC: 1177 AN: 60394

GnomAD4 genome AF: 0.0578 AC: 8794 AN: 152198 Hom.: 778 Cov.: 32 AF XY: 0.0562 AC XY: 4180 AN XY: 74414

African (AFR) AF: 0.187 AC: 7741 AN: 41464

American (AMR) AF: 0.0253 AC: 386 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.0669 AC: 346 AN: 5172

South Asian (SAS) AF: 0.0164 AC: 79 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00156 AC: 106 AN: 68032

Other (OTH) AF: 0.0478 AC: 101 AN: 2114

Alfa AF: 0.0223 Hom.: 876

Bravo AF: 0.0658

Asia WGS AF: 0.0590 AC: 205 AN: 3478

EpiCase AF: 0.00120

EpiControl AF: 0.00101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	6.0
DANN	Benign	0.83
PhyloP100		-0.096
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	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: rs16900617; hg19: chr8-90802491; COSMIC: COSV107275920;