NM_020639.3:c.1476G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_020639.3(RIPK4):c.1476G>A(p.Ala492Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,613,042 control chromosomes in the GnomAD database, including 157,055 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13957 hom., cov: 33)

Exomes 𝑓: 0.44 ( 143098 hom. )

Consequence

RIPK4
NM_020639.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.760

Publications

20 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 21-41741717-C-T is Benign according to our data. Variant chr21-41741717-C-T is described in ClinVar as Benign. ClinVar VariationId is 261348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.76 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK4	NM_020639.3 link	c.1476G>A	p.Ala492Ala	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.1476G>A	p.Ala492Ala	synonymous_variant	Exon 8 of 8	1	NM_020639.3	ENSP00000332454.3		P57078-2
RIPK4	ENST00000352483.3 link	c.1620G>A	p.Ala540Ala	synonymous_variant	Exon 9 of 9	5		ENSP00000330161.2		P57078-1

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

64220

AN:

151974

Hom.:

13955

Cov.:

show subpopulations

Gnomad AFR

AF:

0.322

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.418

Gnomad EAS

AF:

0.597

Gnomad SAS

AF:

0.401

Gnomad FIN

AF:

0.475

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.453

GnomAD2 exomes

AF:

0.447

AC:

112125

AN:

250754

AF XY:

0.447

show subpopulations

Gnomad AFR exome

AF:

0.319

Gnomad AMR exome

AF:

0.465

Gnomad ASJ exome

AF:

0.410

Gnomad EAS exome

AF:

0.590

Gnomad FIN exome

AF:

0.479

Gnomad NFE exome

AF:

0.448

Gnomad OTH exome

AF:

0.459

GnomAD4 exome

AF:

0.441

AC:

644043

AN:

1460950

Hom.:

143098

Cov.:

AF XY:

0.440

AC XY:

319718

AN XY:

726852

show subpopulations

African (AFR)

AF:

0.316

AC:

10594

AN:

33480

American (AMR)

AF:

0.468

AC:

20922

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.406

AC:

10612

AN:

26134

East Asian (EAS)

AF:

0.607

AC:

24086

AN:

39698

South Asian (SAS)

AF:

0.392

AC:

33818

AN:

86258

European-Finnish (FIN)

AF:

0.472

AC:

24802

AN:

52504

Middle Eastern (MID)

AF:

0.406

AC:

2344

AN:

5768

European-Non Finnish (NFE)

AF:

0.441

AC:

490616

AN:

1111996

Other (OTH)

AF:

0.435

AC:

26249

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

27160

54319

81479

108638

135798

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14886

29772

44658

59544

74430

<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:

0.422

AC:

64246

AN:

152092

Hom.:

13957

Cov.:

AF XY:

0.425

AC XY:

31580

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.321

AC:

13332

AN:

41480

American (AMR)

AF:

0.484

AC:

7403

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.418

AC:

1452

AN:

3472

East Asian (EAS)

AF:

0.597

AC:

3089

AN:

5174

South Asian (SAS)

AF:

0.400

AC:

1928

AN:

4824

European-Finnish (FIN)

AF:

0.475

AC:

5021

AN:

10568

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.450

AC:

30583

AN:

67970

Other (OTH)

AF:

0.454

AC:

959

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1873

3747

5620

7494

9367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.438

Hom.:

34228

Bravo

AF:

0.422

Asia WGS

AF:

0.464

AC:

1613

AN:

3478

EpiCase

AF:

0.451

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

Oct 02, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

-0.43

CADD

Benign

5.2

(source)

DANN

Benign

0.89

PhyloP100

-0.76

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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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