Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020639.3(RIPK4):c.*983G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,162 control chromosomes in the GnomAD database, including 11,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11099 hom., cov: 33)

Exomes 𝑓: 0.52 ( 8 hom. )

Consequence

RIPK4
NM_020639.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.98

Publications

6 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 21-41739855-C-T is Benign according to our data. Variant chr21-41739855-C-T is described in ClinVar as Benign. ClinVar VariationId is 339990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020639.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK4	NM_020639.3	MANE Select	c.*983G>A		3_prime_UTR	Exon 8 of 8	NP_065690.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RIPK4	ENST00000332512.8	TSL:1 MANE Select	c.*983G>A	3_prime_UTR	Exon 8 of 8	ENSP00000332454.3
RIPK4	ENST00000352483.3	TSL:5	c.*983G>A	3_prime_UTR	Exon 9 of 9	ENSP00000330161.2
ENSG00000236883	ENST00000423276.1	TSL:3	n.299+184C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.372

AC:

56549

AN:

151994

Hom.:

11096

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.388

Gnomad AMR

AF:

0.444

Gnomad ASJ

AF:

0.408

Gnomad EAS

AF:

0.611

Gnomad SAS

AF:

0.394

Gnomad FIN

AF:

0.412

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.398

Gnomad OTH

AF:

0.404

GnomAD4 exome

AF:

0.520

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.667

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.372

AC:

56569

AN:

152112

Hom.:

11099

Cov.:

AF XY:

0.376

AC XY:

27937

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.255

AC:

10575

AN:

41518

American (AMR)

AF:

0.445

AC:

6793

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.408

AC:

1415

AN:

3468

East Asian (EAS)

AF:

0.611

AC:

3157

AN:

5164

South Asian (SAS)

AF:

0.393

AC:

1895

AN:

4824

European-Finnish (FIN)

AF:

0.412

AC:

4362

AN:

10576

Middle Eastern (MID)

AF:

0.415

AC:

122

AN:

294

European-Non Finnish (NFE)

AF:

0.398

AC:

27042

AN:

67966

Other (OTH)

AF:

0.405

AC:

856

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1807

3614

5422

7229

9036

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.396

Hom.:

15545

Bravo

AF:

0.372

Asia WGS

AF:

0.467

AC:

1621

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bartsocas-Papas syndrome 1 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.43

(source)

DANN

Benign

0.24

PhyloP100

-2.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over