8-89784141-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAA

Variant names:

• chr8-89784141-TAAAA-T
• rs71268283
• NM_003821.6:c.1029+22_1029+25delAAAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000220751.5(RIPK2):​c.1029+3_1029+6delAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 547,146 control chromosomes in the GnomAD database, including 100 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00076 (0 hom., cov: 0)
  • Exomes 𝑓: 0.12 (100 hom.)
• Consequence: RIPK2 ENST00000220751.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 74 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000220751.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK2	NM_003821.6	MANE Select	c.1029+22_1029+25delAAAA		intron	N/A	NP_003812.1
	RIPK2	NM_001375360.1		c.618+22_618+25delAAAA		intron	N/A	NP_001362289.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK2	ENST00000220751.5	TSL:1 MANE Select	c.1029+3_1029+6delAAAA		splice_region intron	N/A	ENSP00000220751.4
	RIPK2	ENST00000522965.1	TSL:1	n.*668+3_*668+6delAAAA		splice_region intron	N/A	ENSP00000429271.1
	RIPK2	ENST00000929530.1		c.1089+3_1089+6delAAAA		splice_region intron	N/A	ENSP00000599589.1

Frequencies

GnomAD3 genomes AF: 0.000763 AC: 74 AN: 97030 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000853

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00112

Gnomad ASJ AF: 0.000358

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000814

Gnomad FIN AF: 0.00345

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000599

Gnomad OTH AF: 0.000780

GnomAD2 exomes AF: 0.0789 AC: 2258 AN: 28604 AF XY: 0.0764

Gnomad AFR exome AF: 0.0663

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.0649

Gnomad EAS exome AF: 0.0531

Gnomad FIN exome AF: 0.0688

Gnomad NFE exome AF: 0.0880

Gnomad OTH exome AF: 0.0866

GnomAD4 exome AF: 0.125 AC: 56156 AN: 450108 Hom.: 100 AF XY: 0.123 AC XY: 28721 AN XY: 234040

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0857 AC: 791 AN: 9230

American (AMR) AF: 0.104 AC: 1111 AN: 10688

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 966 AN: 9984

East Asian (EAS) AF: 0.0473 AC: 946 AN: 19992

South Asian (SAS) AF: 0.0845 AC: 2130 AN: 25206

European-Finnish (FIN) AF: 0.115 AC: 3189 AN: 27678

Middle Eastern (MID) AF: 0.122 AC: 201 AN: 1646

European-Non Finnish (NFE) AF: 0.136 AC: 44217 AN: 324006

Other (OTH) AF: 0.120 AC: 2605 AN: 21678

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000763 AC: 74 AN: 97038 Hom.: 0 Cov.: 0 AF XY: 0.00102 AC XY: 45 AN XY: 44182

African (AFR) AF: 0.000852 AC: 20 AN: 23466

American (AMR) AF: 0.00112 AC: 10 AN: 8918

Ashkenazi Jewish (ASJ) AF: 0.000358 AC: 1 AN: 2792

East Asian (EAS) AF: 0.00 AC: 0 AN: 2856

South Asian (SAS) AF: 0.000818 AC: 2 AN: 2446

European-Finnish (FIN) AF: 0.00345 AC: 9 AN: 2610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 206

European-Non Finnish (NFE) AF: 0.000599 AC: 31 AN: 51732

Other (OTH) AF: 0.000774 AC: 1 AN: 1292

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

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: rs71268283; hg19: chr8-90796369;