chr6-30067312-C-A

Position:

• chr6-30067312-C-A

Variant summary

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

The NM_021959.3(PPP1R11):​c.-99C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0939 in 1,280,210 control chromosomes in the GnomAD database, including 6,447 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 0.086 (649 hom., cov: 32)
  • Exomes 𝑓: 0.095 (5798 hom.)
• Consequence: PPP1R11 NM_021959.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.176

Genes affected

PPP1R11 (HGNC:9285): (protein phosphatase 1 regulatory inhibitor subunit 11) This gene encodes a specific inhibitor of protein phosphatase-1 (PP1) with a differential sensitivity toward the metal-independent and metal-dependent forms of PP1. The gene is located within the major histocompatibility complex class I region on chromosome 6. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R11	NM_021959.3	c.-99C>A		5_prime_UTR_variant	1/3	ENST00000376772.8	NP_068778.1
PPP1R11	XM_047419279.1	c.-99C>A		5_prime_UTR_variant	2/4		XP_047275235.1
PPP1R11	XM_047419280.1	c.-99C>A		5_prime_UTR_variant	3/5		XP_047275236.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R11	ENST00000376772.8	c.-99C>A		5_prime_UTR_variant	1/3	1	NM_021959.3	ENSP00000365963.3
PPP1R11	ENST00000376769.6	c.-330C>A		5_prime_UTR_variant	1/4	2		ENSP00000365960.2
PPP1R11	ENST00000376773.5	c.-88+303C>A		intron_variant		3		ENSP00000365964.1

Frequencies

GnomAD3 genomes AF: 0.0860 AC: 13076 AN: 152110 Hom.: 647 Cov.: 32

Gnomad AFR AF: 0.0638

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0668

Gnomad EAS AF: 0.0387

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0901

Gnomad OTH AF: 0.0915

GnomAD4 exome AF: 0.0949 AC: 107062 AN: 1127984 Hom.: 5798 Cov.: 15 AF XY: 0.0960 AC XY: 54365 AN XY: 566390

Gnomad4 AFR exome AF: 0.0559

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.0616

Gnomad4 EAS exome AF: 0.0626

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.0861

Gnomad4 NFE exome AF: 0.0921

Gnomad4 OTH exome AF: 0.0830

GnomAD4 genome AF: 0.0861 AC: 13100 AN: 152226 Hom.: 649 Cov.: 32 AF XY: 0.0864 AC XY: 6429 AN XY: 74430

Gnomad4 AFR AF: 0.0639

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.0668

Gnomad4 EAS AF: 0.0388

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0778

Gnomad4 NFE AF: 0.0901

Gnomad4 OTH AF: 0.0905

Alfa AF: 0.0769 Hom.: 231

Bravo AF: 0.0907

Asia WGS AF: 0.0720 AC: 249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.6
DANN	Benign	0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1150738; hg19: chr6-30035089;