Variant chr6-3076907-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001354930.2(RIPK1):c.84T>C(p.Phe28=) 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
RIPK1	NM_001354930.2 linkuse as main transcript	c.84T>C	p.Phe28=	synonymous_variant	2/11	ENST00000259808.9	NP_001341859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPK1	ENST00000259808.9 linkuse as main transcript	c.84T>C	p.Phe28=	synonymous_variant	2/11	5	NM_001354930.2	ENSP00000259808	P1	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

GnomAD3 exomes

AF:

0.913

AC:

229559

AN:

251308

Hom.:

105556

AF XY:

0.920

AC XY:

124989

AN XY:

135840

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 SAS exome

AF:

0.942

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

Gnomad4 AFR exome

AF:

0.815

Gnomad4 AMR exome

AF:

0.868

Gnomad4 ASJ exome

AF:

0.984

Gnomad4 EAS exome

AF:

0.742

Gnomad4 SAS exome

AF:

0.945

Gnomad4 FIN exome

AF:

0.903

Gnomad4 NFE exome

AF:

0.963

Gnomad4 OTH exome

AF:

0.933

GnomAD4 genome

AF:

0.904

AC:

136771

AN:

151240

Hom.:

62227

Cov.:

AF XY:

0.902

AC XY:

66649

AN XY:

73882

show subpopulations

Gnomad4 AFR

AF:

0.817

Gnomad4 AMR

AF:

0.907

Gnomad4 ASJ

AF:

0.983

Gnomad4 EAS

AF:

0.735

Gnomad4 SAS

AF:

0.934

Gnomad4 FIN

AF:

0.895

Gnomad4 NFE

AF:

0.963

Gnomad4 OTH

AF:

0.909

Alfa

AF:

0.949

Hom.:

93011

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

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Immunodeficiency 57

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Autoinflammation with episodic fever and lymphadenopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

2.1

DANN

Benign

0.67

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over