chr21-41765605-A-C

Variant names:

• chr21-41765605-A-C
• rs4919944
• NM_020639.3:c.182+1255T>G

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+1255T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 152,204 control chromosomes in the GnomAD database, including 40,106 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 0.72 (40106 hom., cov: 34)
• Consequence: RIPK4 NM_020639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.956
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.82 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+1255T>G		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+1255T>G		intron	N/A	ENSP00000332454.3
	RIPK4	ENST00000352483.3	TSL:5	c.182+1255T>G		intron	N/A	ENSP00000330161.2
	ENSG00000289513	ENST00000827190.1		n.304+476A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109891 AN: 152086 Hom.: 40066 Cov.: 34

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.718

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

GnomAD4 genome AF: 0.723 AC: 109983 AN: 152204 Hom.: 40106 Cov.: 34 AF XY: 0.718 AC XY: 53448 AN XY: 74422

African (AFR) AF: 0.828 AC: 34352 AN: 41506

American (AMR) AF: 0.686 AC: 10483 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 2312 AN: 3472

East Asian (EAS) AF: 0.676 AC: 3500 AN: 5174

South Asian (SAS) AF: 0.653 AC: 3152 AN: 4828

European-Finnish (FIN) AF: 0.664 AC: 7042 AN: 10598

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.689 AC: 46832 AN: 68018

Other (OTH) AF: 0.717 AC: 1516 AN: 2114

Alfa AF: 0.686 Hom.: 33253

Bravo AF: 0.728

Asia WGS AF: 0.673 AC: 2344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.20
DANN	Benign	0.42
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4919944; hg19: chr21-43185765; COSMIC: COSV60188741;