NM_003821.6:c.1029+23_1029+25delAAA

Variant names:

• chr8-89784141-TAAA-T
• rs71268283
• NM_003821.6:c.1029+23_1029+25delAAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003821.6(RIPK2):​c.1029+23_1029+25delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 546,772 control chromosomes in the GnomAD database, including 7,113 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (5666 hom., cov: 0)
  • Exomes 𝑓: 0.23 (1447 hom.)
• Consequence: RIPK2 NM_003821.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.769
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 8-89784141-TAAA-T is Benign according to our data. Variant chr8-89784141-TAAA-T is described in ClinVar as Benign. ClinVar VariationId is 403380.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK2	NM_003821.6	c.1029+23_1029+25delAAA		intron_variant	Intron 8 of 10	ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1	c.618+23_618+25delAAA		intron_variant	Intron 7 of 9		NP_001362289.1
RIPK2	XM_011517357.3	c.516+23_516+25delAAA		intron_variant	Intron 6 of 8		XP_011515659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPK2	ENST00000220751.5	c.1029+23_1029+25delAAA		intron_variant	Intron 8 of 10	1	NM_003821.6	ENSP00000220751.4

Frequencies

GnomAD3 genomes AF: 0.368 AC: 35513 AN: 96464 Hom.: 5668 Cov.: 0

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.0684

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.381

GnomAD2 exomes AF: 0.0786 AC: 2247 AN: 28604 AF XY: 0.0737

Gnomad AFR exome AF: 0.0861

Gnomad AMR exome AF: 0.150

Gnomad ASJ exome AF: 0.0596

Gnomad EAS exome AF: 0.104

Gnomad FIN exome AF: 0.0383

Gnomad NFE exome AF: 0.0738

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.230 AC: 103588 AN: 450302 Hom.: 1447 AF XY: 0.226 AC XY: 52857 AN XY: 233950

African (AFR) AF: 0.154 AC: 1417 AN: 9230

American (AMR) AF: 0.169 AC: 1811 AN: 10736

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 1613 AN: 9966

East Asian (EAS) AF: 0.0900 AC: 1770 AN: 19662

South Asian (SAS) AF: 0.138 AC: 3478 AN: 25156

European-Finnish (FIN) AF: 0.193 AC: 5363 AN: 27722

Middle Eastern (MID) AF: 0.226 AC: 371 AN: 1642

European-Non Finnish (NFE) AF: 0.256 AC: 83110 AN: 324510

Other (OTH) AF: 0.215 AC: 4655 AN: 21678

GnomAD4 genome AF: 0.368 AC: 35504 AN: 96470 Hom.: 5666 Cov.: 0 AF XY: 0.366 AC XY: 16079 AN XY: 43924

African (AFR) AF: 0.230 AC: 5365 AN: 23306

American (AMR) AF: 0.391 AC: 3460 AN: 8860

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 873 AN: 2780

East Asian (EAS) AF: 0.0682 AC: 194 AN: 2846

South Asian (SAS) AF: 0.280 AC: 682 AN: 2434

European-Finnish (FIN) AF: 0.570 AC: 1497 AN: 2628

Middle Eastern (MID) AF: 0.427 AC: 88 AN: 206

European-Non Finnish (NFE) AF: 0.439 AC: 22599 AN: 51430

Other (OTH) AF: 0.381 AC: 482 AN: 1266

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.77
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: rs71268283; hg19: chr8-90796369; COSMIC: COSV55132790; COSMIC: COSV55132790;