NM_020639.3:c.1548C>T

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.1548C>T(p.Asp516Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 1,613,212 control chromosomes in the GnomAD database, including 305,174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 23812 hom., cov: 34)

Exomes 𝑓: 0.62 ( 281362 hom. )

Consequence

RIPK4
NM_020639.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.397

Publications

17 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=-0.56).

BP6

Variant 21-41741645-G-A is Benign according to our data. Variant chr21-41741645-G-A is described in ClinVar as Benign. ClinVar VariationId is 261349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.397 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK4	NM_020639.3 link	c.1548C>T	p.Asp516Asp	synonymous_variant	Exon 8 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.1548C>T	p.Asp516Asp	synonymous_variant	Exon 8 of 8	1	NM_020639.3	ENSP00000332454.3		P57078-2
RIPK4	ENST00000352483.3 link	c.1692C>T	p.Asp564Asp	synonymous_variant	Exon 9 of 9	5		ENSP00000330161.2		P57078-1

Frequencies

GnomAD3 genomes

AF:

0.540

AC:

82148

AN:

152018

Hom.:

23819

Cov.:

show subpopulations

Gnomad AFR

AF:

0.307

Gnomad AMI

AF:

0.688

Gnomad AMR

AF:

0.621

Gnomad ASJ

AF:

0.662

Gnomad EAS

AF:

0.629

Gnomad SAS

AF:

0.637

Gnomad FIN

AF:

0.620

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.629

Gnomad OTH

AF:

0.581

GnomAD2 exomes

AF:

0.608

AC:

152476

AN:

250904

AF XY:

0.617

show subpopulations

Gnomad AFR exome

AF:

0.298

Gnomad AMR exome

AF:

0.611

Gnomad ASJ exome

AF:

0.648

Gnomad EAS exome

AF:

0.618

Gnomad FIN exome

AF:

0.623

Gnomad NFE exome

AF:

0.633

Gnomad OTH exome

AF:

0.635

GnomAD4 exome

AF:

0.618

AC:

903029

AN:

1461076

Hom.:

281362

Cov.:

AF XY:

0.620

AC XY:

450825

AN XY:

726904

show subpopulations

African (AFR)

AF:

0.296

AC:

9919

AN:

33480

American (AMR)

AF:

0.612

AC:

27390

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.648

AC:

16946

AN:

26134

East Asian (EAS)

AF:

0.632

AC:

25107

AN:

39700

South Asian (SAS)

AF:

0.640

AC:

55246

AN:

86258

European-Finnish (FIN)

AF:

0.615

AC:

32420

AN:

52688

Middle Eastern (MID)

AF:

0.640

AC:

3693

AN:

5768

European-Non Finnish (NFE)

AF:

0.626

AC:

695828

AN:

1111946

Other (OTH)

AF:

0.604

AC:

36480

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

24432

48865

73297

97730

122162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18552

37104

55656

74208

92760

<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:

0.540

AC:

82156

AN:

152136

Hom.:

23812

Cov.:

AF XY:

0.543

AC XY:

40419

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.306

AC:

12710

AN:

41504

American (AMR)

AF:

0.622

AC:

9513

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.662

AC:

2300

AN:

3472

East Asian (EAS)

AF:

0.629

AC:

3245

AN:

5160

South Asian (SAS)

AF:

0.636

AC:

3071

AN:

4832

European-Finnish (FIN)

AF:

0.620

AC:

6561

AN:

10586

Middle Eastern (MID)

AF:

0.646

AC:

190

AN:

294

European-Non Finnish (NFE)

AF:

0.629

AC:

42713

AN:

67958

Other (OTH)

AF:

0.579

AC:

1226

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1812

3624

5436

7248

9060

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

710

1420

2130

2840

3550

<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:

0.603

Hom.:

44813

Bravo

AF:

0.533

Asia WGS

AF:

0.588

AC:

2045

AN:

3478

EpiCase

AF:

0.638

EpiControl

AF:

0.638

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Bartsocas-Papas syndrome 1

Benign:2

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. -

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.56

CADD

Benign

6.7

(source)

DANN

Benign

0.86

PhyloP100

0.40

Mutation Taster

=98/2

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