chr21-41741990-G-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.1203C>T(p.Gly401Gly) 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 1,586,898 control chromosomes in the GnomAD database, including 154,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13939 hom., cov: 33)

Exomes 𝑓: 0.44 ( 140806 hom. )

Consequence

RIPK4
NM_020639.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.02

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=-0.64).

BP6

Variant 21-41741990-G-A is Benign according to our data. Variant chr21-41741990-G-A is described in ClinVar as Benign. ClinVar VariationId is 261347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.02 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.1203C>T	p.Gly401Gly	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.1203C>T	p.Gly401Gly	synonymous_variant	Exon 8 of 8	1	NM_020639.3	ENSP00000332454.3		P57078-2
RIPK4	ENST00000352483.3 link	c.1347C>T	p.Gly449Gly	synonymous_variant	Exon 9 of 9	5		ENSP00000330161.2		P57078-1

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

64154

AN:

151934

Hom.:

13936

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.392

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.418

Gnomad EAS

AF:

0.596

Gnomad SAS

AF:

0.400

Gnomad FIN

AF:

0.475

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.453

GnomAD2 exomes

AF:

0.450

AC:

104023

AN:

230908

AF XY:

0.451

show subpopulations

Gnomad AFR exome

AF:

0.318

Gnomad AMR exome

AF:

0.467

Gnomad ASJ exome

AF:

0.417

Gnomad EAS exome

AF:

0.592

Gnomad FIN exome

AF:

0.478

Gnomad NFE exome

AF:

0.450

Gnomad OTH exome

AF:

0.460

GnomAD4 exome

AF:

0.441

AC:

632949

AN:

1434846

Hom.:

140806

Cov.:

AF XY:

0.440

AC XY:

312643

AN XY:

710038

show subpopulations

African (AFR)

AF:

0.316

AC:

10417

AN:

32962

American (AMR)

AF:

0.469

AC:

20349

AN:

43414

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

9920

AN:

24356

East Asian (EAS)

AF:

0.607

AC:

23896

AN:

39358

South Asian (SAS)

AF:

0.392

AC:

32190

AN:

82104

European-Finnish (FIN)

AF:

0.472

AC:

24429

AN:

51714

Middle Eastern (MID)

AF:

0.406

AC:

2295

AN:

5654

European-Non Finnish (NFE)

AF:

0.441

AC:

483692

AN:

1096090

Other (OTH)

AF:

0.435

AC:

25761

AN:

59194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

16837

33674

50512

67349

84186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14844

29688

44532

59376

74220

<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:

64179

AN:

152052

Hom.:

13939

Cov.:

AF XY:

0.424

AC XY:

31538

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.320

AC:

13295

AN:

41484

American (AMR)

AF:

0.484

AC:

7401

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.418

AC:

1452

AN:

3470

East Asian (EAS)

AF:

0.597

AC:

3070

AN:

5146

South Asian (SAS)

AF:

0.398

AC:

1920

AN:

4820

European-Finnish (FIN)

AF:

0.475

AC:

5028

AN:

10584

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.450

AC:

30574

AN:

67952

Other (OTH)

AF:

0.454

AC:

958

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1869

3738

5608

7477

9346

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:

0.440

Hom.:

58734

Bravo

AF:

0.422

Asia WGS

AF:

0.464

AC:

1613

AN:

3478

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

- -

Oct 02, 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

-0.64

CADD

Benign

7.5

(source)

DANN

Benign

0.88

PhyloP100

1.0

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