rs1107110

chr14-94265573-A-Gchr14-94265573-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_058237.2(PPP4R4):c.2284+100A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,058,674 control chromosomes in the GnomAD database, including 24,170 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 0.20 (3696 hom., cov: 32)
  • Exomes 𝑓: 0.19 (20474 hom.)
• Consequence: PPP4R4 NM_058237.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198

Genes affected

PPP4R4 (HGNC:23788): (protein phosphatase 4 regulatory subunit 4) The protein encoded by this gene is a HEAT-like repeat-containing protein. The HEAT repeat is a tandemly repeated, 37-47 amino acid long module occurring in a number of cytoplasmic proteins. Arrays of HEAT repeats form a rod-like helical structure and appear to function as protein-protein interaction surfaces. The repeat-containing region of this protein has some similarity to the constant regulatory domain of the protein phosphatase 2A PR65/A subunit. The encoded protein binds protein serine/threonine phosphatase 4c in the cytoplasm. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP4R4	NM_058237.2	c.2284+100A>G		intron_variant		ENST00000304338.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP4R4	ENST00000304338.8	c.2284+100A>G		intron_variant		1	NM_058237.2	P1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31071 AN: 151948 Hom.: 3695 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.207

GnomAD4 exome AF: 0.194 AC: 175649 AN: 906608 Hom.: 20474 AF XY: 0.195 AC XY: 91106 AN XY: 466440

Gnomad4 AFR exome AF: 0.237

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.587

Gnomad4 SAS exome AF: 0.256

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.166

Gnomad4 OTH exome AF: 0.207

GnomAD4 genome AF: 0.204 AC: 31096 AN: 152066 Hom.: 3696 Cov.: 32 AF XY: 0.209 AC XY: 15570 AN XY: 74336

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.588

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.206

Alfa AF: 0.114 Hom.: 196

Bravo AF: 0.204

Asia WGS AF: 0.367 AC: 1274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.6
Dann	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs1107110; hg19: chr14-94731910; COSMIC: COSV58553107;