NM_020639.3:c.360A>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020639.3(RIPK4):c.360A>C(p.Arg120Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,613,896 control chromosomes in the GnomAD database, including 15,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1590 hom., cov: 33)

Exomes 𝑓: 0.14 ( 14345 hom. )

Consequence

RIPK4
NM_020639.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.630

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

Bartsocas-Papas syndrome 1
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
ectodermal dysplasia syndrome
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics

RIPK4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 21-41756639-T-G is Benign according to our data. Variant chr21-41756639-T-G is described in ClinVar as Benign. ClinVar VariationId is 340031.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.63 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK4	NM_020639.3 link	c.360A>C	p.Arg120Arg	synonymous_variant	Exon 2 of 8	ENST00000332512.8	NP_065690.2	Q9H4D1Q96T11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPK4	ENST00000332512.8 link	c.360A>C	p.Arg120Arg	synonymous_variant	Exon 2 of 8	1	NM_020639.3	ENSP00000332454.3		P57078-2
RIPK4	ENST00000352483.3 link	c.360A>C	p.Arg120Arg	synonymous_variant	Exon 2 of 9	5		ENSP00000330161.2		P57078-1

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21191

AN:

152052

Hom.:

1593

Cov.:

show subpopulations

Gnomad AFR

AF:

0.167

Gnomad AMI

AF:

0.124

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.210

Gnomad EAS

AF:

0.0369

Gnomad SAS

AF:

0.187

Gnomad FIN

AF:

0.0840

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.155

GnomAD2 exomes

AF:

0.129

AC:

32464

AN:

251304

AF XY:

0.135

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.0740

Gnomad ASJ exome

AF:

0.209

Gnomad EAS exome

AF:

0.0329

Gnomad FIN exome

AF:

0.0860

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.135

AC:

197880

AN:

1461726

Hom.:

14345

Cov.:

AF XY:

0.138

AC XY:

100476

AN XY:

727168

show subpopulations

African (AFR)

AF:

0.170

AC:

5706

AN:

33480

American (AMR)

AF:

0.0786

AC:

3517

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

5472

AN:

26136

East Asian (EAS)

AF:

0.0284

AC:

1129

AN:

39700

South Asian (SAS)

AF:

0.194

AC:

16707

AN:

86258

European-Finnish (FIN)

AF:

0.0861

AC:

4585

AN:

53270

Middle Eastern (MID)

AF:

0.227

AC:

1307

AN:

5768

European-Non Finnish (NFE)

AF:

0.136

AC:

150700

AN:

1111994

Other (OTH)

AF:

0.145

AC:

8757

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

10524

21048

31573

42097

52621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5402

10804

16206

21608

27010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.139

AC:

21200

AN:

152170

Hom.:

1590

Cov.:

AF XY:

0.136

AC XY:

10111

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.167

AC:

6922

AN:

41518

American (AMR)

AF:

0.124

AC:

1890

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.210

AC:

728

AN:

3462

East Asian (EAS)

AF:

0.0364

AC:

188

AN:

5170

South Asian (SAS)

AF:

0.187

AC:

903

AN:

4822

European-Finnish (FIN)

AF:

0.0840

AC:

890

AN:

10596

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9177

AN:

67986

Other (OTH)

AF:

0.154

AC:

325

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

959

1917

2876

3834

4793

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

240

480

720

960

1200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.139

Hom.:

2472

Bravo

AF:

0.142

Asia WGS

AF:

0.118

AC:

412

AN:

3478

EpiCase

AF:

0.147

EpiControl

AF:

0.148

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Bartsocas-Papas syndrome 1

Benign:2

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 05, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

(source)

DANN

Benign

0.38

PhyloP100

-0.63

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over