21-41764437-G-A

Variant names:

• chr21-41764437-G-A
• rs2309107
• NM_020639.3:c.182+2423C>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+2423C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,976 control chromosomes in the GnomAD database, including 6,204 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 (6204 hom., cov: 32)
• Consequence: RIPK4 NM_020639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.80
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK4	NM_020639.3	c.182+2423C>T		intron_variant	Intron 1 of 7	ENST00000332512.8	NP_065690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPK4	ENST00000332512.8	c.182+2423C>T		intron_variant	Intron 1 of 7	1	NM_020639.3	ENSP00000332454.3
RIPK4	ENST00000352483.3	c.182+2423C>T		intron_variant	Intron 1 of 8	5		ENSP00000330161.2

Frequencies

GnomAD3 genomes AF: 0.277 AC: 41989 AN: 151858 Hom.: 6203 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.0370

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.276 AC: 42011 AN: 151976 Hom.: 6204 Cov.: 32 AF XY: 0.268 AC XY: 19892 AN XY: 74278

African (AFR) AF: 0.349 AC: 14454 AN: 41432

American (AMR) AF: 0.220 AC: 3369 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 947 AN: 3466

East Asian (EAS) AF: 0.0365 AC: 189 AN: 5174

South Asian (SAS) AF: 0.245 AC: 1175 AN: 4796

European-Finnish (FIN) AF: 0.196 AC: 2074 AN: 10574

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19000 AN: 67940

Other (OTH) AF: 0.264 AC: 557 AN: 2106

Alfa AF: 0.276 Hom.: 22972

Bravo AF: 0.280

Asia WGS AF: 0.152 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.091
DANN	Benign	0.41
PhyloP100		-3.8
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: rs2309107; hg19: chr21-43184597;