21-41739813-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020639.3(RIPK4):​c.*1025G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00483 in 152,356 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 3 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RIPK4
NM_020639.3 3_prime_UTR

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.325
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 21-41739813-C-A is Benign according to our data. Variant chr21-41739813-C-A is described in ClinVar as [Benign]. Clinvar id is 895208.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00483 (736/152356) while in subpopulation NFE AF= 0.0077 (524/68032). AF 95% confidence interval is 0.00716. There are 3 homozygotes in gnomad4. There are 360 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RIPK4NM_020639.3 linkc.*1025G>T 3_prime_UTR_variant Exon 8 of 8 ENST00000332512.8 NP_065690.2 Q9H4D1Q96T11

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RIPK4ENST00000332512 linkc.*1025G>T 3_prime_UTR_variant Exon 8 of 8 1 NM_020639.3 ENSP00000332454.3 P57078-2
RIPK4ENST00000352483 linkc.*1025G>T 3_prime_UTR_variant Exon 9 of 9 5 ENSP00000330161.2 P57078-1
ENSG00000236883ENST00000423276.1 linkn.299+142C>A intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
AF:
0.00484
AC:
737
AN:
152238
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00118
Gnomad AMI
AF:
0.00219
Gnomad AMR
AF:
0.00569
Gnomad ASJ
AF:
0.00720
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00290
Gnomad FIN
AF:
0.00179
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.00770
Gnomad OTH
AF:
0.00669
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
88
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
66
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00483
AC:
736
AN:
152356
Hom.:
3
Cov.:
33
AF XY:
0.00483
AC XY:
360
AN XY:
74510
show subpopulations
Gnomad4 AFR
AF:
0.00118
Gnomad4 AMR
AF:
0.00568
Gnomad4 ASJ
AF:
0.00720
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00290
Gnomad4 FIN
AF:
0.00179
Gnomad4 NFE
AF:
0.00770
Gnomad4 OTH
AF:
0.00662
Alfa
AF:
0.00503
Hom.:
1
Bravo
AF:
0.00510
Asia WGS
AF:
0.00260
AC:
10
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Bartsocas-Papas syndrome 1 Benign:1
Apr 27, 2017
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
1.2
DANN
Benign
0.75

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

LitVar

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

Other links and lift over

dbSNP: rs73216989; hg19: chr21-43159973; API