chr6-3086772-C-G

Variant names:

• chr6-3086772-C-G
• rs9391981
• NM_001354930.2:c.838+1364C>G

Variant summary

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

The NM_001354930.2(RIPK1):​c.838+1364C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,156 control chromosomes in the GnomAD database, including 47,718 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 0.74 (47718 hom., cov: 32)
• Consequence: RIPK1 NM_001354930.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 7 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK1	NM_001354930.2	c.838+1364C>G		intron_variant	Intron 6 of 10	ENST00000259808.9	NP_001341859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPK1	ENST00000259808.9	c.838+1364C>G		intron_variant	Intron 6 of 10	5	NM_001354930.2	ENSP00000259808.3

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112561 AN: 152038 Hom.: 47715 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.948

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.948

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.740 AC: 112588 AN: 152156 Hom.: 47718 Cov.: 32 AF XY: 0.741 AC XY: 55156 AN XY: 74412

African (AFR) AF: 0.292 AC: 12116 AN: 41478

American (AMR) AF: 0.828 AC: 12663 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3177 AN: 3468

East Asian (EAS) AF: 0.744 AC: 3838 AN: 5160

South Asian (SAS) AF: 0.850 AC: 4104 AN: 4826

European-Finnish (FIN) AF: 0.892 AC: 9456 AN: 10598

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.948 AC: 64474 AN: 68028

Other (OTH) AF: 0.780 AC: 1644 AN: 2108

Alfa AF: 0.777 Hom.: 3451

Bravo AF: 0.714

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.42
DANN	Benign	0.62
PhyloP100		-0.13
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: rs9391981; hg19: chr6-3087006;