Genetic Variant RIPK4:c.*782_*783dupAG (chr21-41740054-A-ACT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_020639.3(RIPK4):c.*782_*783dupAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.41 ( 13192 hom., cov: 0)

Exomes 𝑓: 0.40 ( 0 hom. )

Consequence

RIPK4
NM_020639.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.113

Publications

0 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 -10 ACMG points.

BP6

Variant 21-41740054-A-ACT is Benign according to our data. Variant chr21-41740054-A-ACT is described in ClinVar as [Benign]. Clinvar id is 339992.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK4	NM_020639.3 link	c.782_783dupAG		3_prime_UTR_variant	Exon 8 of 8	ENST00000332512.8	NP_065690.2	Q9H4D1Q96T11

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RIPK4	ENST00000332512.8 link	c.782_783dupAG	3_prime_UTR_variant	Exon 8 of 8	1	NM_020639.3	ENSP00000332454.3	P57078-2
RIPK4	ENST00000352483.3 link	c.782_783dupAG	3_prime_UTR_variant	Exon 9 of 9	5		ENSP00000330161.2	P57078-1
ENSG00000236883	ENST00000423276.1 link	n.299+384_299+385dupCT	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.407

AC:

61668

AN:

151696

Hom.:

13192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.265

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.477

Gnomad ASJ

AF:

0.423

Gnomad EAS

AF:

0.609

Gnomad SAS

AF:

0.405

Gnomad FIN

AF:

0.472

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.438

GnomAD4 exome

AF:

0.400

AC:

AN:

Hom.:

Cov.:

AF XY:

0.375

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.003830), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.406

AC:

61684

AN:

151814

Hom.:

13192

Cov.:

AF XY:

0.410

AC XY:

30413

AN XY:

74184

show subpopulations

African (AFR)

AF:

0.264

AC:

10945

AN:

41418

American (AMR)

AF:

0.477

AC:

7284

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.423

AC:

1465

AN:

3464

East Asian (EAS)

AF:

0.609

AC:

3124

AN:

5126

South Asian (SAS)

AF:

0.403

AC:

1941

AN:

4814

European-Finnish (FIN)

AF:

0.472

AC:

4974

AN:

10528

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.450

AC:

30549

AN:

67892

Other (OTH)

AF:

0.439

AC:

922

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1818

3636

5454

7272

9090

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.417

Hom.:

1647

Bravo

AF:

0.403

Asia WGS

AF:

0.472

AC:

1640

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Popliteal pterygium syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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21-41740054-A-ACT

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