chr21-41740097-C-T

Position:

• chr21-41740097-C-T

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.*741G>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 0.0184 in 152,128 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (40 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RIPK4 NM_020639.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.31

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=-0.95).
• BP6: Variant 21-41740097-C-T is Benign according to our data. Variant chr21-41740097-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 339994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0184 (2803/152128) while in subpopulation SAS AF= 0.0411 (198/4814). AF 95% confidence interval is 0.0364. There are 40 homozygotes in gnomad4. There are 1373 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 40 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPK4	NM_020639.3	c.*741G>A		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.*741G>A		3_prime_UTR_variant	8/8	1	NM_020639.3	ENSP00000332454	P1
	ENST00000423276.1	n.299+426C>T		intron_variant, non_coding_transcript_variant		3
RIPK4	ENST00000352483.3	c.*741G>A		3_prime_UTR_variant	9/9	5		ENSP00000330161

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2804 AN: 152010 Hom.: 40 Cov.: 33

Gnomad AFR AF: 0.00350

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0209

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0411

Gnomad FIN AF: 0.0216

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0244

Gnomad OTH AF: 0.0273

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0184 AC: 2803 AN: 152128 Hom.: 40 Cov.: 33 AF XY: 0.0185 AC XY: 1373 AN XY: 74368

Gnomad4 AFR AF: 0.00349

Gnomad4 AMR AF: 0.0209

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0411

Gnomad4 FIN AF: 0.0216

Gnomad4 NFE AF: 0.0244

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0209 Hom.: 20

Bravo AF: 0.0171

Asia WGS AF: 0.0180 AC: 64 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Bartsocas-Papas syndrome 1 Benign:1

Likely 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

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- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
DANN	Benign	0.61

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: rs13050509; hg19: chr21-43160257;