NM_020639.3:c.182+660C>T

Variant names:

• chr21-41766200-G-A
• rs55860816
• NM_020639.3:c.182+660C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

RIPK4 Gene-Disease associations (from GenCC):

• Bartsocas-Papas syndrome 1

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• ectodermal dysplasia syndrome

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics

ENSG00000289513 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020639.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK4	NM_020639.3	MANE Select	c.182+660C>T		intron	N/A	NP_065690.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK4	ENST00000332512.8	TSL:1 MANE Select	c.182+660C>T		intron	N/A	ENSP00000332454.3
	RIPK4	ENST00000352483.3	TSL:5	c.182+660C>T		intron	N/A	ENSP00000330161.2
	ENSG00000289513	ENST00000827190.1		n.304+1071G>A		intron	N/A

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

African (AFR) AF: 0.362 AC: 15026 AN: 41482

American (AMR) AF: 0.221 AC: 3377 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 913 AN: 3464

East Asian (EAS) AF: 0.0349 AC: 181 AN: 5186

South Asian (SAS) AF: 0.242 AC: 1168 AN: 4826

European-Finnish (FIN) AF: 0.197 AC: 2096 AN: 10614

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.279 AC: 18946 AN: 67972

Other (OTH) AF: 0.268 AC: 565 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.84
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs55860816; hg19: chr21-43186360;