rs3171532

chr21-41739855-C-Tchr21-41739855-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020639.3(RIPK4):c.*983G>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 0.372 in 152,162 control chromosomes in the GnomAD database, including 11,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (11099 hom., cov: 33)
  • Exomes 𝑓: 0.52 (8 hom.)
• Consequence: RIPK4 NM_020639.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.98

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 21-41739855-C-T is Benign according to our data. Variant chr21-41739855-C-T is described in ClinVar as [Benign]. Clinvar id is 339990.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIPK4	NM_020639.3	c.*983G>A		3_prime_UTR_variant	8/8	ENST00000332512.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIPK4	ENST00000332512.8	c.*983G>A		3_prime_UTR_variant	8/8	1	NM_020639.3	P1
	ENST00000423276.1	n.299+184C>T		intron_variant, non_coding_transcript_variant		3
RIPK4	ENST00000352483.3	c.*983G>A		3_prime_UTR_variant	9/9	5

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56549 AN: 151994 Hom.: 11096 Cov.: 33

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.520 AC: 26 AN: 50 Hom.: 8 Cov.: 0 AF XY: 0.500 AC XY: 16 AN XY: 32

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.372 AC: 56569 AN: 152112 Hom.: 11099 Cov.: 33 AF XY: 0.376 AC XY: 27937 AN XY: 74370

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.405

Alfa AF: 0.403 Hom.: 12527

Bravo AF: 0.372

Asia WGS AF: 0.467 AC: 1621 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.43
Dann	Benign	0.24

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: rs3171532; hg19: chr21-43160015;