14-94265573-A-G

Variant names:

• chr14-94265573-A-G
• rs1107110
• NM_058237.2:c.2284+100A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058237.2. 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
	PPP4R4	NM_058237.2	MANE Select	c.2284+100A>G		intron	N/A	NP_478144.1
	PPP4R4	NM_001348142.2		c.2041+100A>G		intron	N/A	NP_001335071.1
	PPP4R4	NM_001348143.2		c.1963+100A>G		intron	N/A	NP_001335072.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP4R4	ENST00000304338.8	TSL:1 MANE Select	c.2284+100A>G		intron	N/A	ENSP00000305924.3

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

African (AFR) AF: 0.237 AC: 4843 AN: 20412

American (AMR) AF: 0.163 AC: 5480 AN: 33632

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 3376 AN: 19700

East Asian (EAS) AF: 0.587 AC: 20278 AN: 34556

South Asian (SAS) AF: 0.256 AC: 16424 AN: 64064

European-Finnish (FIN) AF: 0.192 AC: 9570 AN: 49974

Middle Eastern (MID) AF: 0.236 AC: 1067 AN: 4524

European-Non Finnish (NFE) AF: 0.166 AC: 106041 AN: 638436

Other (OTH) AF: 0.207 AC: 8570 AN: 41310

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

African (AFR) AF: 0.235 AC: 9747 AN: 41472

American (AMR) AF: 0.153 AC: 2341 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 616 AN: 3464

East Asian (EAS) AF: 0.588 AC: 3031 AN: 5156

South Asian (SAS) AF: 0.253 AC: 1218 AN: 4812

European-Finnish (FIN) AF: 0.209 AC: 2210 AN: 10582

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11261 AN: 67974

Other (OTH) AF: 0.206 AC: 436 AN: 2114

Alfa AF: 0.119 Hom.: 217

Bravo AF: 0.204

Asia WGS AF: 0.367 AC: 1274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.68
PhyloP100		-0.20
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: rs1107110; hg19: chr14-94731910; COSMIC: COSV58553107;