NM_020639.3:c.2331G>A

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.2331G>A(p.Thr777Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,608,350 control chromosomes in the GnomAD database, including 157,386 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14016 hom., cov: 33)

Exomes 𝑓: 0.44 ( 143370 hom. )

Consequence

RIPK4
NM_020639.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.49

Publications

11 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:

ENSG00000236883 (HGNC:):

ENSG00000236883 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=-0.93).

BP6

Variant 21-41740862-C-T is Benign according to our data. Variant chr21-41740862-C-T is described in ClinVar as [Benign]. Clinvar id is 261351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.49 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK4	NM_020639.3 link	c.2331G>A	p.Thr777Thr	synonymous_variant	Exon 8 of 8	ENST00000332512.8	NP_065690.2	Q9H4D1Q96T11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RIPK4	ENST00000332512.8 link	c.2331G>A	p.Thr777Thr	synonymous_variant	Exon 8 of 8	1	NM_020639.3	ENSP00000332454.3	P57078-2
RIPK4	ENST00000352483.3 link	c.2475G>A	p.Thr825Thr	synonymous_variant	Exon 9 of 9	5		ENSP00000330161.2	P57078-1
ENSG00000236883	ENST00000423276.1 link	n.300-285C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

64272

AN:

151924

Hom.:

14014

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.483

Gnomad ASJ

AF:

0.436

Gnomad EAS

AF:

0.608

Gnomad SAS

AF:

0.403

Gnomad FIN

AF:

0.475

Gnomad MID

AF:

0.420

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.452

GnomAD2 exomes

AF:

0.449

AC:

109646

AN:

243950

AF XY:

0.449

show subpopulations

Gnomad AFR exome

AF:

0.316

Gnomad AMR exome

AF:

0.466

Gnomad ASJ exome

AF:

0.429

Gnomad EAS exome

AF:

0.604

Gnomad FIN exome

AF:

0.478

Gnomad NFE exome

AF:

0.449

Gnomad OTH exome

AF:

0.459

GnomAD4 exome

AF:

0.442

AC:

643395

AN:

1456308

Hom.:

143370

Cov.:

AF XY:

0.441

AC XY:

319220

AN XY:

724108

show subpopulations

African (AFR)

AF:

0.316

AC:

10544

AN:

33392

American (AMR)

AF:

0.469

AC:

20835

AN:

44470

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

11085

AN:

25960

East Asian (EAS)

AF:

0.620

AC:

24583

AN:

39630

South Asian (SAS)

AF:

0.394

AC:

33869

AN:

85914

European-Finnish (FIN)

AF:

0.473

AC:

24267

AN:

51324

Middle Eastern (MID)

AF:

0.413

AC:

2293

AN:

5558

European-Non Finnish (NFE)

AF:

0.441

AC:

489641

AN:

1109880

Other (OTH)

AF:

0.437

AC:

26278

AN:

60180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

20903

41806

62710

83613

104516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.423

AC:

64296

AN:

152042

Hom.:

14016

Cov.:

AF XY:

0.425

AC XY:

31596

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.320

AC:

13294

AN:

41496

American (AMR)

AF:

0.484

AC:

7397

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.436

AC:

1514

AN:

3470

East Asian (EAS)

AF:

0.608

AC:

3129

AN:

5146

South Asian (SAS)

AF:

0.401

AC:

1939

AN:

4830

European-Finnish (FIN)

AF:

0.475

AC:

5014

AN:

10554

Middle Eastern (MID)

AF:

0.418

AC:

122

AN:

292

European-Non Finnish (NFE)

AF:

0.450

AC:

30578

AN:

67946

Other (OTH)

AF:

0.453

AC:

955

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1873

3746

5619

7492

9365

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.432

Hom.:

4420

Bravo

AF:

0.423

Asia WGS

AF:

0.470

AC:

1634

AN:

3478

EpiCase

AF:

0.452

EpiControl

AF:

0.453

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

- -

Nov 12, 2018

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

-0.93

CADD

Benign

0.027

(source)

DANN

Benign

0.70

PhyloP100

-3.5

Mutation Taster

=100/0

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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NM_020639.3:c.2331G>A

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