rs3850705

Variant names:

• chr21-41760048-C-G
• rs3850705
• NM_020639.3:c.183-3232G>C

Your query was ambiguous. Multiple possible variants found:

• chr21-41760048-C-G
• chr21-41760048-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020639.3(RIPK4):​c.183-3232G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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.183-3232G>C		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.183-3232G>C		intron	N/A	ENSP00000332454.3
	RIPK4	ENST00000352483.3	TSL:5	c.183-3232G>C		intron	N/A	ENSP00000330161.2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.075
DANN	Benign	0.72
PhyloP100		-2.3

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;