6-3076907-T-C

Variant names:

• chr6-3076907-T-C
• rs2272990
• NM_001354930.2:c.84T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.23

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]

ACMG classification

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 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 rank	MANE	Protein	UniProt
RIPK1	NM_001354930.2	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	c.84T>C	p.Phe28Phe	synonymous_variant	Exon 2 of 11	5	NM_001354930.2	ENSP00000259808.3

Frequencies

GnomAD3 genomes AF: 0.904 AC: 136675 AN: 151124 Hom.: 62187 Cov.: 25

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

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.: 33 AF XY: 0.947 AC XY: 688539 AN XY: 726770

Gnomad4 AFR exome AF: 0.815 AC: 27248 AN: 33438

Gnomad4 AMR exome AF: 0.868 AC: 38778 AN: 44700

Gnomad4 ASJ exome AF: 0.984 AC: 25697 AN: 26126

Gnomad4 EAS exome AF: 0.742 AC: 29449 AN: 39682

Gnomad4 SAS exome AF: 0.945 AC: 81444 AN: 86206

Gnomad4 FIN exome AF: 0.903 AC: 48205 AN: 53408

Gnomad4 NFE exome AF: 0.963 AC: 1070124 AN: 1111148

Gnomad4 Remaining exome AF: 0.933 AC: 56305 AN: 60356

GnomAD4 genome AF: 0.904 AC: 136771 AN: 151240 Hom.: 62227 Cov.: 25 AF XY: 0.902 AC XY: 66649 AN XY: 73882

Gnomad4 AFR AF: 0.817 AC: 0.817087 AN: 0.817087

Gnomad4 AMR AF: 0.907 AC: 0.907139 AN: 0.907139

Gnomad4 ASJ AF: 0.983 AC: 0.982997 AN: 0.982997

Gnomad4 EAS AF: 0.735 AC: 0.734949 AN: 0.734949

Gnomad4 SAS AF: 0.934 AC: 0.933599 AN: 0.933599

Gnomad4 FIN AF: 0.895 AC: 0.894626 AN: 0.894626

Gnomad4 NFE AF: 0.963 AC: 0.963445 AN: 0.963445

Gnomad4 OTH AF: 0.909 AC: 0.908571 AN: 0.908571

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

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
DANN	Benign	0.67
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

Publications

LitVar

Other links and lift over

dbSNP: rs2272990; hg19: chr6-3077141; COSMIC: COSV108063273;