rs6596945

Positions:

• chr6-3071679-C-A
• chr6-3071679-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001354930.2(RIPK1):​c.-61+3018C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,966 control chromosomes in the GnomAD database, including 6,366 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 0.27 (6366 hom., cov: 33)
• Consequence: RIPK1 NM_001354930.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIPK1	NM_001354930.2	c.-61+3018C>A		intron_variant		ENST00000259808.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIPK1	ENST00000259808.9	c.-61+3018C>A		intron_variant		5	NM_001354930.2	P1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41682 AN: 151848 Hom.: 6358 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.275 AC: 41725 AN: 151966 Hom.: 6366 Cov.: 33 AF XY: 0.274 AC XY: 20380 AN XY: 74266

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.251

Alfa AF: 0.214 Hom.: 5400

Bravo AF: 0.286

Asia WGS AF: 0.262 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.63

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: rs6596945; hg19: chr6-3071913;