rs12209182

Positions:

• chr6-3111722-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.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

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]

LOC107986556 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPK1	NM_001354930.2	c.1729+767C>T		intron_variant		ENST00000259808.9	NP_001341859.1
LOC107986556	XR_001743928.3	n.860-2326G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPK1	ENST00000259808.9	c.1729+767C>T		intron_variant		5	NM_001354930.2	ENSP00000259808	P1

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

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.468

Alfa AF: 0.512 Hom.: 4823

Bravo AF: 0.402

Asia WGS AF: 0.307 AC: 1069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.77

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: rs12209182; hg19: chr6-3111956;