Variant rs2277789 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_020639.3(RIPK4):c.1005G>T(p.Leu335=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,610,980 control chromosomes in the GnomAD database, including 135,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11485 hom., cov: 32)

Exomes 𝑓: 0.41 ( 123629 hom. )

Consequence

RIPK4
NM_020639.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.13

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 21-41744072-C-A is Benign according to our data. Variant chr21-41744072-C-A is described in ClinVar as [Benign]. Clinvar id is 261346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIPK4	NM_020639.3 linkuse as main transcript	c.1005G>T	p.Leu335=	synonymous_variant	7/8	ENST00000332512.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIPK4	ENST00000332512.8 linkuse as main transcript	c.1005G>T	p.Leu335=	synonymous_variant	7/8	1	NM_020639.3	P1	P57078-2
RIPK4	ENST00000352483.3 linkuse as main transcript	c.1149G>T	p.Leu383=	synonymous_variant	8/9	5			P57078-1

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

58042

AN:

151854

Hom.:

11485

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.504

Gnomad SAS

AF:

0.336

Gnomad FIN

AF:

0.412

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.426

Gnomad OTH

AF:

0.404

GnomAD3 exomes

AF:

0.403

AC:

99572

AN:

246868

Hom.:

20463

AF XY:

0.402

AC XY:

53888

AN XY:

133918

show subpopulations

Gnomad AFR exome

AF:

0.268

Gnomad AMR exome

AF:

0.419

Gnomad ASJ exome

AF:

0.362

Gnomad EAS exome

AF:

0.506

Gnomad SAS exome

AF:

0.319

Gnomad FIN exome

AF:

0.419

Gnomad NFE exome

AF:

0.424

Gnomad OTH exome

AF:

0.417

GnomAD4 exome

AF:

0.410

AC:

598276

AN:

1459008

Hom.:

123629

Cov.:

AF XY:

0.408

AC XY:

296033

AN XY:

725580

show subpopulations

Gnomad4 AFR exome

AF:

0.266

Gnomad4 AMR exome

AF:

0.424

Gnomad4 ASJ exome

AF:

0.360

Gnomad4 EAS exome

AF:

0.504

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.418

Gnomad4 NFE exome

AF:

0.419

Gnomad4 OTH exome

AF:

0.398

GnomAD4 genome

AF:

0.382

AC:

58066

AN:

151972

Hom.:

11485

Cov.:

AF XY:

0.383

AC XY:

28463

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.271

Gnomad4 AMR

AF:

0.443

Gnomad4 ASJ

AF:

0.368

Gnomad4 EAS

AF:

0.504

Gnomad4 SAS

AF:

0.335

Gnomad4 FIN

AF:

0.412

Gnomad4 NFE

AF:

0.426

Gnomad4 OTH

AF:

0.405

Alfa

AF:

0.397

Hom.:

6878

Bravo

AF:

0.383

Asia WGS

AF:

0.389

AC:

1349

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Bartsocas-Papas syndrome 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

6.8

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over