rs6596945

Variant names:

• chr6-3071679-C-A
• rs6596945
• NM_001354930.2:c.-61+3018C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-3071679-C-A
• chr6-3071679-C-T

Variant summary

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

The NM_001354930.2(RIPK1):​c.-61+3018C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,966 control chromosomes in the GnomAD database, including 6,366 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 0.27 (6366 hom., cov: 33)
• Consequence: RIPK1 NM_001354930.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• Publications: 15 publications found

Genes affected

RIPK1 (HGNC:10019): (receptor interacting serine/threonine kinase 1) This gene encodes a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. The encoded protein plays a role in inflammation and cell death in response to tissue damage, pathogen recognition, and as part of developmental regulation. RIPK1/RIPK3 kinase-mediated necrosis is referred to as necroptosis. Genetic disruption of this gene in mice results in death shortly after birth. [provided by RefSeq, Aug 2017]

RIPK1 Gene-Disease associations (from GenCC):

• immunodeficiency 57

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autoinflammation with episodic fever and lymphadenopathy

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354930.2. 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
	RIPK1	NM_001354930.2	MANE Select	c.-61+3018C>A		intron	N/A	NP_001341859.1	Q13546-1
	RIPK1	NM_003804.6		c.-60-5085C>A		intron	N/A	NP_003795.2	Q13546-1
	RIPK1	NM_001354931.2		c.-60-5085C>A		intron	N/A	NP_001341860.1	Q13546-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK1	ENST00000259808.9	TSL:5 MANE Select	c.-61+3018C>A		intron	N/A	ENSP00000259808.3	Q13546-1
	RIPK1	ENST00000380409.3	TSL:1	c.-60-5085C>A		intron	N/A	ENSP00000369773.3	Q13546-2
	RIPK1	ENST00000967583.1		c.-61+3018C>A		intron	N/A	ENSP00000637642.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41682 AN: 151848 Hom.: 6358 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.275 AC: 41725 AN: 151966 Hom.: 6366 Cov.: 33 AF XY: 0.274 AC XY: 20380 AN XY: 74266

African (AFR) AF: 0.412 AC: 17070 AN: 41394

American (AMR) AF: 0.241 AC: 3690 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 640 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1477 AN: 5156

South Asian (SAS) AF: 0.250 AC: 1204 AN: 4822

European-Finnish (FIN) AF: 0.231 AC: 2434 AN: 10546

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14074 AN: 67986

Other (OTH) AF: 0.251 AC: 529 AN: 2110

Alfa AF: 0.222 Hom.: 8824

Bravo AF: 0.286

Asia WGS AF: 0.262 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.63
PhyloP100		0.068
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: rs6596945; hg19: chr6-3071913;