rs55860816

Positions:

• chr21-41766200-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020639.3(RIPK4):​c.182+660C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,154 control chromosomes in the GnomAD database, including 6,394 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6394 hom., cov: 33)
• Consequence: RIPK4 NM_020639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPK4	NM_020639.3	c.182+660C>T		intron_variant		ENST00000332512.8	NP_065690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPK4	ENST00000332512.8	c.182+660C>T		intron_variant		1	NM_020639.3	ENSP00000332454.3
RIPK4	ENST00000352483.3	c.182+660C>T		intron_variant		5		ENSP00000330161.2

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42499 AN: 152034 Hom.: 6394 Cov.: 33

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.0354

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.260

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.270

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.279 AC: 42521 AN: 152154 Hom.: 6394 Cov.: 33 AF XY: 0.271 AC XY: 20132 AN XY: 74394

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.0349

Gnomad4 SAS AF: 0.242

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.268

Alfa AF: 0.283 Hom.: 812

Bravo AF: 0.283

Asia WGS AF: 0.155 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.84

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: rs55860816; hg19: chr21-43186360;