21-41739813-C-A

Position:

• chr21-41739813-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.325

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]

(HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
RIPK4	NM_020639.3	c.*1025G>T		3_prime_UTR_variant	8/8	ENST00000332512.8	NP_065690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPK4	ENST00000332512.8	c.*1025G>T		3_prime_UTR_variant	8/8	1	NM_020639.3	ENSP00000332454	P1
	ENST00000423276.1	n.299+142C>A		intron_variant, non_coding_transcript_variant		3
RIPK4	ENST00000352483.3	c.*1025G>T		3_prime_UTR_variant	9/9	5		ENSP00000330161

Frequencies

GnomAD3 genomes AF: 0.00484 AC: 737 AN: 152238 Hom.: 3 Cov.: 33

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

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

Submissions by phenotype

Bartsocas-Papas syndrome 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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

Other links and lift over

dbSNP: rs73216989; hg19: chr21-43159973;