rs724165

Positions:

• chr14-24337023-G-A

Variant summary

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

The NM_006871.4(RIPK3):​c.1275+63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 1,603,026 control chromosomes in the GnomAD database, including 240,554 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 0.44 (17229 hom., cov: 32)
  • Exomes 𝑓: 0.54 (223325 hom.)
• Consequence: RIPK3 NM_006871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

Genes affected

RIPK3 (HGNC:10021): (receptor interacting serine/threonine kinase 3) The product of this gene is a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases, and contains a C-terminal domain unique from other RIP family members. The encoded protein is predominantly localized to the cytoplasm, and can undergo nucleocytoplasmic shuttling dependent on novel nuclear localization and export signals. It is a component of the tumor necrosis factor (TNF) receptor-I signaling complex, and can induce apoptosis and weakly activate the NF-kappaB transcription factor. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIPK3	NM_006871.4	c.1275+63C>T		intron_variant		ENST00000216274.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIPK3	ENST00000216274.10	c.1275+63C>T		intron_variant		1	NM_006871.4	P1
RIPK3	ENST00000554756.1	c.*617+63C>T		intron_variant, NMD_transcript_variant		1
RIPK3	ENST00000554569.1	c.317+63C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66650 AN: 151918 Hom.: 17227 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.461

GnomAD4 exome AF: 0.544 AC: 789038 AN: 1450990 Hom.: 223325 Cov.: 39 AF XY: 0.542 AC XY: 390486 AN XY: 720642

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.376

Gnomad4 ASJ exome AF: 0.573

Gnomad4 EAS exome AF: 0.175

Gnomad4 SAS exome AF: 0.391

Gnomad4 FIN exome AF: 0.565

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.515

GnomAD4 genome AF: 0.439 AC: 66668 AN: 152036 Hom.: 17229 Cov.: 32 AF XY: 0.436 AC XY: 32391 AN XY: 74312

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.455

Alfa AF: 0.492 Hom.: 2978

Bravo AF: 0.415

Asia WGS AF: 0.256 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.53

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: rs724165; hg19: chr14-24806229; COSMIC: COSV53475123; COSMIC: COSV53475123;