rs1114832

Variant names:

• chr19-45132943-C-T
• rs1114832
• NM_019121.2:c.203-5571C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019121.2(PPP1R37):​c.203-5571C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 152,220 control chromosomes in the GnomAD database, including 775 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 0.092 (775 hom., cov: 32)
• Consequence: PPP1R37 NM_019121.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805
• Publications: 17 publications found

Genes affected

PPP1R37 (HGNC:27607): (protein phosphatase 1 regulatory subunit 37) Predicted to enable protein phosphatase inhibitor activity. Predicted to be involved in negative regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]

MARK4 (HGNC:13538): (microtubule affinity regulating kinase 4) This gene encodes a member of the microtubule affinity-regulating kinase family. These protein kinases phosphorylate microtubule-associated proteins and regulate the transition between stable and dynamic microtubules. The encoded protein is associated with the centrosome throughout mitosis and may be involved in cell cycle control. Expression of this gene is a potential marker for cancer, and the encoded protein may also play a role in Alzheimer's disease. Pseudogenes of this gene are located on both the short and long arm of chromosome 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

MARK4 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019121.2. 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
	PPP1R37	NM_019121.2	MANE Select	c.203-5571C>T		intron	N/A	NP_061994.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R37	ENST00000221462.9	TSL:5 MANE Select	c.203-5571C>T		intron	N/A	ENSP00000221462.3
	PPP1R37	ENST00000544069.2	TSL:5	c.203-7563C>T		intron	N/A	ENSP00000445252.1
	MARK4	ENST00000587566.5	TSL:5	c.-277+53566C>T		intron	N/A	ENSP00000465414.1

Frequencies

GnomAD3 genomes AF: 0.0921 AC: 14004 AN: 152102 Hom.: 773 Cov.: 32

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0973

Gnomad ASJ AF: 0.0757

Gnomad EAS AF: 0.0608

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0977

Gnomad OTH AF: 0.0852

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

GnomAD4 genome AF: 0.0921 AC: 14013 AN: 152220 Hom.: 775 Cov.: 32 AF XY: 0.0981 AC XY: 7298 AN XY: 74398

African (AFR) AF: 0.0540 AC: 2242 AN: 41538

American (AMR) AF: 0.0975 AC: 1492 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0757 AC: 263 AN: 3472

East Asian (EAS) AF: 0.0606 AC: 314 AN: 5182

South Asian (SAS) AF: 0.131 AC: 632 AN: 4824

European-Finnish (FIN) AF: 0.204 AC: 2154 AN: 10572

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0977 AC: 6648 AN: 68016

Other (OTH) AF: 0.0886 AC: 187 AN: 2110

Alfa AF: 0.0936 Hom.: 1236

Bravo AF: 0.0799

Asia WGS AF: 0.103 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.86
PhyloP100		-0.81
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: rs1114832; hg19: chr19-45636201;