NM_001354930.2:c.84T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001354930.2(RIPK1):c.84T>C(p.Phe28Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 1,611,990 control chromosomes in the GnomAD database, including 718,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 62227 hom., cov: 25)

Exomes 𝑓: 0.95 ( 656133 hom. )

Consequence

RIPK1
NM_001354930.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.23

Publications

38 publications found

Variant links:

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

RIPK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 6-3076907-T-C is Benign according to our data. Variant chr6-3076907-T-C is described in ClinVar as Benign. ClinVar VariationId is 1166905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK1	NM_001354930.2 link	c.84T>C	p.Phe28Phe	synonymous_variant	Exon 2 of 11	ENST00000259808.9	NP_001341859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPK1	ENST00000259808.9 link	c.84T>C	p.Phe28Phe	synonymous_variant	Exon 2 of 11	5	NM_001354930.2	ENSP00000259808.3		Q13546-1

Frequencies

GnomAD3 genomes

AF:

0.904

AC:

136675

AN:

151124

Hom.:

62187

Cov.:

show subpopulations

Gnomad AFR

AF:

0.817

Gnomad AMI

AF:

0.961

Gnomad AMR

AF:

0.907

Gnomad ASJ

AF:

0.983

Gnomad EAS

AF:

0.735

Gnomad SAS

AF:

0.934

Gnomad FIN

AF:

0.895

Gnomad MID

AF:

0.968

Gnomad NFE

AF:

0.963

Gnomad OTH

AF:

0.910

GnomAD2 exomes

AF:

0.913

AC:

229559

AN:

251308

AF XY:

0.920

show subpopulations

Gnomad AFR exome

AF:

0.815

Gnomad AMR exome

AF:

0.859

Gnomad ASJ exome

AF:

0.983

Gnomad EAS exome

AF:

0.726

Gnomad FIN exome

AF:

0.899

Gnomad NFE exome

AF:

0.962

Gnomad OTH exome

AF:

0.941

GnomAD4 exome

AF:

0.947

AC:

1382687

AN:

1460750

Hom.:

656133

Cov.:

AF XY:

0.947

AC XY:

688539

AN XY:

726770

show subpopulations

African (AFR)

AF:

0.815

AC:

27248

AN:

33438

American (AMR)

AF:

0.868

AC:

38778

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.984

AC:

25697

AN:

26126

East Asian (EAS)

AF:

0.742

AC:

29449

AN:

39682

South Asian (SAS)

AF:

0.945

AC:

81444

AN:

86206

European-Finnish (FIN)

AF:

0.903

AC:

48205

AN:

53408

Middle Eastern (MID)

AF:

0.956

AC:

5437

AN:

5686

European-Non Finnish (NFE)

AF:

0.963

AC:

1070124

AN:

1111148

Other (OTH)

AF:

0.933

AC:

56305

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

3681

7363

11044

14726

18407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21584

43168

64752

86336

107920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.904

AC:

136771

AN:

151240

Hom.:

62227

Cov.:

AF XY:

0.902

AC XY:

66649

AN XY:

73882

show subpopulations

African (AFR)

AF:

0.817

AC:

33530

AN:

41036

American (AMR)

AF:

0.907

AC:

13774

AN:

15184

Ashkenazi Jewish (ASJ)

AF:

0.983

AC:

3411

AN:

3470

East Asian (EAS)

AF:

0.735

AC:

3760

AN:

5116

South Asian (SAS)

AF:

0.934

AC:

4457

AN:

4774

European-Finnish (FIN)

AF:

0.895

AC:

9356

AN:

10458

Middle Eastern (MID)

AF:

0.969

AC:

283

AN:

292

European-Non Finnish (NFE)

AF:

0.963

AC:

65416

AN:

67898

Other (OTH)

AF:

0.909

AC:

1908

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

578

1157

1735

2314

2892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.946

Hom.:

124852

Bravo

AF:

0.898

Asia WGS

AF:

0.840

AC:

2921

AN:

3478

EpiCase

AF:

0.961

EpiControl

AF:

0.963

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. -

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Immunodeficiency 57

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autoinflammation with episodic fever and lymphadenopathy

Benign:1

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.1

(source)

DANN

Benign

0.67

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over