NM_020639.3:c.*983G>A

Variant names:

• chr21-41739855-C-T
• rs3171532
• NM_020639.3:c.*983G>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.*983G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,162 control chromosomes in the GnomAD database, including 11,107 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 0.37 (11099 hom., cov: 33)
  • Exomes 𝑓: 0.52 (8 hom.)
• Consequence: RIPK4 NM_020639.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.98
• Publications: 6 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

ENSG00000236883 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK4	NM_020639.3	c.*983G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000332512.8	NP_065690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPK4	ENST00000332512.8	c.*983G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_020639.3	ENSP00000332454.3
RIPK4	ENST00000352483.3	c.*983G>A		3_prime_UTR_variant	Exon 9 of 9	5		ENSP00000330161.2
ENSG00000236883	ENST00000423276.1	n.299+184C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56549 AN: 151994 Hom.: 11096 Cov.: 33

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.404

GnomAD4 exome AF: 0.520 AC: 26 AN: 50 Hom.: 8 Cov.: 0 AF XY: 0.500 AC XY: 16 AN XY: 32

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.500 AC: 17 AN: 34

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.372 AC: 56569 AN: 152112 Hom.: 11099 Cov.: 33 AF XY: 0.376 AC XY: 27937 AN XY: 74370

African (AFR) AF: 0.255 AC: 10575 AN: 41518

American (AMR) AF: 0.445 AC: 6793 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1415 AN: 3468

East Asian (EAS) AF: 0.611 AC: 3157 AN: 5164

South Asian (SAS) AF: 0.393 AC: 1895 AN: 4824

European-Finnish (FIN) AF: 0.412 AC: 4362 AN: 10576

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27042 AN: 67966

Other (OTH) AF: 0.405 AC: 856 AN: 2112

Alfa AF: 0.396 Hom.: 15545

Bravo AF: 0.372

Asia WGS AF: 0.467 AC: 1621 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Bartsocas-Papas syndrome 1 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.43
DANN	Benign	0.24
PhyloP100		-2.0
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: rs3171532; hg19: chr21-43160015;