rs724165

Variant names:

• chr14-24337023-G-A
• rs724165
• NM_006871.4:c.1275+63C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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]

ENSG00000258973 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RIPK3	NM_006871.4	c.1275+63C>T		intron_variant	Intron 8 of 9	ENST00000216274.10	NP_006862.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPK3	ENST00000216274.10	c.1275+63C>T		intron_variant	Intron 8 of 9	1	NM_006871.4	ENSP00000216274.5
RIPK3	ENST00000554756.1	n.*617+63C>T		intron_variant	Intron 8 of 9	1		ENSP00000452328.1
RIPK3	ENST00000554569.1	c.315+63C>T		intron_variant	Intron 1 of 1	2		ENSP00000451840.1
ENSG00000258973	ENST00000555591.1	n.297+63C>T		intron_variant	Intron 1 of 3	4

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

African (AFR) AF: 0.162 AC: 5361 AN: 33182

American (AMR) AF: 0.376 AC: 16537 AN: 44020

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 14508 AN: 25312

East Asian (EAS) AF: 0.175 AC: 6903 AN: 39538

South Asian (SAS) AF: 0.391 AC: 33309 AN: 85176

European-Finnish (FIN) AF: 0.565 AC: 29939 AN: 53032

Middle Eastern (MID) AF: 0.581 AC: 3318 AN: 5708

European-Non Finnish (NFE) AF: 0.587 AC: 648315 AN: 1105172

Other (OTH) AF: 0.515 AC: 30848 AN: 59850

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

African (AFR) AF: 0.182 AC: 7541 AN: 41464

American (AMR) AF: 0.442 AC: 6749 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2057 AN: 3472

East Asian (EAS) AF: 0.154 AC: 795 AN: 5172

South Asian (SAS) AF: 0.374 AC: 1800 AN: 4818

European-Finnish (FIN) AF: 0.575 AC: 6073 AN: 10570

Middle Eastern (MID) AF: 0.630 AC: 184 AN: 292

European-Non Finnish (NFE) AF: 0.588 AC: 39961 AN: 67960

Other (OTH) AF: 0.455 AC: 960 AN: 2110

Alfa AF: 0.478 Hom.: 6211

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
PhyloP100		-0.17
PromoterAI		0.0090	Neutral
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

Other links and lift over

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