Variant chr21-41766883-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_020639.3(RIPK4):c.159G>A(p.Ser53=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,609,716 control chromosomes in the GnomAD database, including 16,468 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S53S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.14 ( 1554 hom., cov: 33)

Exomes 𝑓: 0.14 ( 14914 hom. )

Consequence

RIPK4
NM_020639.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0540

Variant links:

Genes affected

RIPK4 (HGNC:496): (receptor interacting serine/threonine kinase 4) The protein encoded by this gene is a serine/threonine protein kinase that interacts with protein kinase C-delta. The encoded protein can also activate NFkappaB and is required for keratinocyte differentiation. This kinase undergoes autophosphorylation. [provided by RefSeq, Jul 2008]

RIPK4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 21-41766883-C-T is Benign according to our data. Variant chr21-41766883-C-T is described in ClinVar as [Benign]. Clinvar id is 340036.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-41766883-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIPK4	NM_020639.3 linkuse as main transcript	c.159G>A	p.Ser53=	synonymous_variant	1/8	ENST00000332512.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIPK4	ENST00000332512.8 linkuse as main transcript	c.159G>A	p.Ser53=	synonymous_variant	1/8	1	NM_020639.3	P1	P57078-2
RIPK4	ENST00000352483.3 linkuse as main transcript	c.159G>A	p.Ser53=	synonymous_variant	1/9	5			P57078-1

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20854

AN:

151928

Hom.:

1551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.183

Gnomad AMI

AF:

0.0681

Gnomad AMR

AF:

0.0973

Gnomad ASJ

AF:

0.0611

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0502

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.0510

Gnomad NFE

AF:

0.145

Gnomad OTH

AF:

0.116

GnomAD3 exomes

AF:

0.106

AC:

25347

AN:

239656

Hom.:

1710

AF XY:

0.105

AC XY:

13792

AN XY:

131546

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.0579

Gnomad ASJ exome

AF:

0.0645

Gnomad EAS exome

AF:

0.000452

Gnomad SAS exome

AF:

0.0601

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.108

GnomAD4 exome

AF:

0.137

AC:

199172

AN:

1457676

Hom.:

14914

Cov.:

AF XY:

0.133

AC XY:

96794

AN XY:

725122

show subpopulations

Gnomad4 AFR exome

AF:

0.186

Gnomad4 AMR exome

AF:

0.0632

Gnomad4 ASJ exome

AF:

0.0650

Gnomad4 EAS exome

AF:

0.000203

Gnomad4 SAS exome

AF:

0.0609

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.152

Gnomad4 OTH exome

AF:

0.125

GnomAD4 genome

AF:

0.137

AC:

20866

AN:

152040

Hom.:

1554

Cov.:

AF XY:

0.132

AC XY:

9792

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.183

Gnomad4 AMR

AF:

0.0971

Gnomad4 ASJ

AF:

0.0611

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0498

Gnomad4 FIN

AF:

0.112

Gnomad4 NFE

AF:

0.145

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.131

Hom.:

2887

Bravo

AF:

0.138

Asia WGS

AF:

0.0360

AC:

126

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 02, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Bartsocas-Papas syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.97

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over