rs7278103

Variant names:

• chr21-41743128-C-A
• rs7278103
• NM_020639.3:c.1195+754G>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.1195+754G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,120 control chromosomes in the GnomAD database, including 1,269 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 0.12 (1269 hom., cov: 32)
• Consequence: RIPK4 NM_020639.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK4	NM_020639.3	c.1195+754G>T		intron_variant	Intron 7 of 7	ENST00000332512.8	NP_065690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPK4	ENST00000332512.8	c.1195+754G>T		intron_variant	Intron 7 of 7	1	NM_020639.3	ENSP00000332454.3
RIPK4	ENST00000352483.3	c.1339+754G>T		intron_variant	Intron 8 of 8	5		ENSP00000330161.2

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18246 AN: 152002 Hom.: 1273 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.0531

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.120 AC: 18239 AN: 152120 Hom.: 1269 Cov.: 32 AF XY: 0.122 AC XY: 9059 AN XY: 74346

African (AFR) AF: 0.136 AC: 5637 AN: 41510

American (AMR) AF: 0.105 AC: 1605 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 228 AN: 3472

East Asian (EAS) AF: 0.301 AC: 1549 AN: 5140

South Asian (SAS) AF: 0.0521 AC: 250 AN: 4796

European-Finnish (FIN) AF: 0.175 AC: 1848 AN: 10580

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6815 AN: 68010

Other (OTH) AF: 0.129 AC: 273 AN: 2116

Alfa AF: 0.102 Hom.: 326

Bravo AF: 0.117

Asia WGS AF: 0.166 AC: 574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.53
DANN	Benign	0.77
PhyloP100		-1.9
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: rs7278103; hg19: chr21-43163288;