21-41760048-C-T

Variant names:

• chr21-41760048-C-T
• rs3850705
• NM_020639.3:c.183-3232G>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.183-3232G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,090 control chromosomes in the GnomAD database, including 43,456 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 0.75 (43456 hom., cov: 32)
• Consequence: RIPK4 NM_020639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK4	NM_020639.3	c.183-3232G>A		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.183-3232G>A		intron_variant	Intron 1 of 7	1	NM_020639.3	ENSP00000332454.3
RIPK4	ENST00000352483.3	c.183-3232G>A		intron_variant	Intron 1 of 8	5		ENSP00000330161.2

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114622 AN: 151972 Hom.: 43424 Cov.: 32

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.754 AC: 114705 AN: 152090 Hom.: 43456 Cov.: 32 AF XY: 0.750 AC XY: 55791 AN XY: 74350

African (AFR) AF: 0.820 AC: 34028 AN: 41498

American (AMR) AF: 0.737 AC: 11272 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2423 AN: 3472

East Asian (EAS) AF: 0.672 AC: 3456 AN: 5146

South Asian (SAS) AF: 0.683 AC: 3286 AN: 4810

European-Finnish (FIN) AF: 0.716 AC: 7578 AN: 10584

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.738 AC: 50187 AN: 67976

Other (OTH) AF: 0.747 AC: 1572 AN: 2104

Alfa AF: 0.754 Hom.: 6381

Bravo AF: 0.760

Asia WGS AF: 0.688 AC: 2396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.089
DANN	Benign	0.57
PhyloP100		-2.3
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: rs3850705; hg19: chr21-43180208;