rs55812846

Positions:

chr21-41741309-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_020639.3(RIPK4):c.1884C>T(p.Ser628=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0053 in 1,608,500 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 8 hom., cov: 35)

Exomes 𝑓: 0.0054 ( 34 hom. )

Consequence

RIPK4
NM_020639.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -4.91

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 21-41741309-G-A is Benign according to our data. Variant chr21-41741309-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 191165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-41741309-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.91 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00474 (722/152298) while in subpopulation NFE AF= 0.00541 (368/68010). AF 95% confidence interval is 0.00496. There are 8 homozygotes in gnomad4. There are 343 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPK4	NM_020639.3 linkuse as main transcript	c.1884C>T	p.Ser628=	synonymous_variant	8/8	ENST00000332512.8	NP_065690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPK4	ENST00000332512.8 linkuse as main transcript	c.1884C>T	p.Ser628=	synonymous_variant	8/8	1	NM_020639.3	ENSP00000332454	P1	P57078-2
RIPK4	ENST00000352483.3 linkuse as main transcript	c.2028C>T	p.Ser676=	synonymous_variant	9/9	5		ENSP00000330161		P57078-1
	ENST00000423276.1 linkuse as main transcript			downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00474

AC:

722

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.0681

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00541

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00538

AC:

1310

AN:

243718

Hom.:

AF XY:

0.00546

AC XY:

724

AN XY:

132720

show subpopulations

Gnomad AFR exome

AF:

0.00133

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.0105

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.0152

Gnomad NFE exome

AF:

0.00724

Gnomad OTH exome

AF:

0.00398

GnomAD4 exome

AF:

0.00536

AC:

7803

AN:

1456202

Hom.:

Cov.:

AF XY:

0.00526

AC XY:

3813

AN XY:

724708

show subpopulations

Gnomad4 AFR exome

AF:

0.000867

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.00989

Gnomad4 EAS exome

AF:

0.00123

Gnomad4 SAS exome

AF:

0.00113

Gnomad4 FIN exome

AF:

0.0136

Gnomad4 NFE exome

AF:

0.00568

Gnomad4 OTH exome

AF:

0.00444

GnomAD4 genome

AF:

0.00474

AC:

722

AN:

152298

Hom.:

Cov.:

AF XY:

0.00461

AC XY:

343

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0132

Gnomad4 NFE

AF:

0.00541

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00649

Hom.:

Bravo

AF:

0.00420

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00567

EpiControl

AF:

0.00545

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Sep 28, 2016

- -

Bartsocas-Papas syndrome 1

Benign:1

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

RIPK4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 19, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.32

DANN

Benign

0.87

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