rs1114832

Positions:

• chr19-45132943-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R37	NM_019121.2	c.203-5571C>T		intron_variant		ENST00000221462.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R37	ENST00000221462.9	c.203-5571C>T		intron_variant		5	NM_019121.2	P1
PPP1R37	ENST00000544069.2	c.203-7563C>T		intron_variant		5
MARK4	ENST00000587566.5	c.-277+53566C>T		intron_variant		5
PPP1R37	ENST00000544897.5	n.218-5571C>T		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.0540

Gnomad4 AMR AF: 0.0975

Gnomad4 ASJ AF: 0.0757

Gnomad4 EAS AF: 0.0606

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.0977

Gnomad4 OTH AF: 0.0886

Alfa AF: 0.0955 Hom.: 994

Bravo AF: 0.0799

Asia WGS AF: 0.103 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.86

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: rs1114832; hg19: chr19-45636201;