chr6-3111722-C-T

Variant names:

• chr6-3111722-C-T
• rs12209182
• NM_001354930.2:c.1729+767C>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.1729+767C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 152,138 control chromosomes in the GnomAD database, including 16,682 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 0.43 (16682 hom., cov: 33)
• Consequence: RIPK1 NM_001354930.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366
• Publications: 5 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

LOC107986556 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.582 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK1	NM_001354930.2	MANE Select	c.1729+767C>T		intron	N/A	NP_001341859.1
	RIPK1	NM_003804.6		c.1729+767C>T		intron	N/A	NP_003795.2
	RIPK1	NM_001354931.2		c.1591+767C>T		intron	N/A	NP_001341860.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK1	ENST00000259808.9	TSL:5 MANE Select	c.1729+767C>T		intron	N/A	ENSP00000259808.3
	RIPK1	ENST00000380409.3	TSL:1	c.1591+767C>T		intron	N/A	ENSP00000369773.3
	RIPK1	ENST00000676591.1		n.*1273+767C>T		intron	N/A	ENSP00000504592.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65127 AN: 152020 Hom.: 16691 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.428 AC: 65129 AN: 152138 Hom.: 16682 Cov.: 33 AF XY: 0.426 AC XY: 31671 AN XY: 74350

African (AFR) AF: 0.169 AC: 7030 AN: 41512

American (AMR) AF: 0.386 AC: 5897 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1924 AN: 3472

East Asian (EAS) AF: 0.213 AC: 1106 AN: 5184

South Asian (SAS) AF: 0.326 AC: 1575 AN: 4824

European-Finnish (FIN) AF: 0.576 AC: 6085 AN: 10556

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.587 AC: 39888 AN: 67992

Other (OTH) AF: 0.468 AC: 989 AN: 2114

Alfa AF: 0.509 Hom.: 33261

Bravo AF: 0.402

Asia WGS AF: 0.307 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.77
PhyloP100		-0.37
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: rs12209182; hg19: chr6-3111956;