chr21-41760326-C-T

Variant names:

• chr21-41760326-C-T
• rs3827219
• NM_020639.3:c.183-3510G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020639.3(RIPK4):​c.183-3510G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,238 control chromosomes in the GnomAD database, including 1,974 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 0.16 (1974 hom., cov: 33)
• Consequence: RIPK4 NM_020639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233
• Publications: 1 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.232 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.183-3510G>A		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.183-3510G>A		intron	N/A	ENSP00000332454.3
	RIPK4	ENST00000352483.3	TSL:5	c.183-3510G>A		intron	N/A	ENSP00000330161.2

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23593 AN: 152120 Hom.: 1979 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.0365

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.155 AC: 23600 AN: 152238 Hom.: 1974 Cov.: 33 AF XY: 0.152 AC XY: 11347 AN XY: 74446

African (AFR) AF: 0.162 AC: 6741 AN: 41522

American (AMR) AF: 0.142 AC: 2174 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 890 AN: 3470

East Asian (EAS) AF: 0.0360 AC: 187 AN: 5192

South Asian (SAS) AF: 0.243 AC: 1173 AN: 4820

European-Finnish (FIN) AF: 0.105 AC: 1118 AN: 10604

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10738 AN: 68014

Other (OTH) AF: 0.175 AC: 371 AN: 2114

Alfa AF: 0.155 Hom.: 354

Bravo AF: 0.155

Asia WGS AF: 0.148 AC: 516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.55
PhyloP100		-0.23
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: rs3827219; hg19: chr21-43180486;