rs41309096

Positions:

chr2-230212439-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_080424.4(SP110):c.584-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,582,472 control chromosomes in the GnomAD database, including 50,454 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5799 hom., cov: 32)

Exomes 𝑓: 0.25 ( 44655 hom. )

Consequence

SP110
NM_080424.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002188

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.176

Variant links:

Genes affected

SP110 (HGNC:5401): (SP110 nuclear body protein) The nuclear body is a multiprotein complex that may have a role in the regulation of gene transcription. This gene is a member of the SP100/SP140 family of nuclear body proteins and encodes a leukocyte-specific nuclear body component. The protein can function as an activator of gene transcription and may serve as a nuclear hormone receptor coactivator. In addition, it has been suggested that the protein may play a role in ribosome biogenesis and in the induction of myeloid cell differentiation. Alternative splicing has been observed for this gene and three transcript variants, encoding distinct isoforms, have been identified. [provided by RefSeq, Jul 2008]

SP110 links:

SP140 (HGNC:17133): (SP140 nuclear body protein) This gene encodes a member of the SP100 family of proteins, which are share common domains including an N-terminal homogeneously staining region domain followed by a SP100/autoimmune regulator/NucP41/P75/deformed epidermal autoregulatory factor domain, a plant homeobox zinc finger, and a bromodomain. The encoded protein is interferon-inducible and is expressed at high levels in the nuclei of leukocytes. Variants of this gene have been associated with multiple sclerosis, Crohn's disease, and chronic lymphocytic leukemia. Alternative splicing results in multiple variants. [provided by RefSeq, Aug 2016]

SP140 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 2-230212439-G-A is Benign according to our data. Variant chr2-230212439-G-A is described in ClinVar as [Benign]. Clinvar id is 334912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP110	NM_080424.4 linkuse as main transcript	c.584-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000258381.11	NP_536349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11 linkuse as main transcript	c.584-9C>T		splice_polypyrimidine_tract_variant, intron_variant		2	NM_080424.4	ENSP00000258381	P1	Q9HB58-6

Frequencies

GnomAD3 genomes

AF:

0.269

AC:

40875

AN:

151922

Hom.:

5788

Cov.:

show subpopulations

Gnomad AFR

AF:

0.339

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.253

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.0974

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.298

GnomAD3 exomes

AF:

0.238

AC:

59759

AN:

250638

Hom.:

7453

AF XY:

0.237

AC XY:

32148

AN XY:

135422

show subpopulations

Gnomad AFR exome

AF:

0.344

Gnomad AMR exome

AF:

0.260

Gnomad ASJ exome

AF:

0.310

Gnomad EAS exome

AF:

0.0854

Gnomad SAS exome

AF:

0.202

Gnomad FIN exome

AF:

0.207

Gnomad NFE exome

AF:

0.250

Gnomad OTH exome

AF:

0.258

GnomAD4 exome

AF:

0.246

AC:

351895

AN:

1430432

Hom.:

44655

Cov.:

AF XY:

0.246

AC XY:

175123

AN XY:

713312

show subpopulations

Gnomad4 AFR exome

AF:

0.344

Gnomad4 AMR exome

AF:

0.259

Gnomad4 ASJ exome

AF:

0.312

Gnomad4 EAS exome

AF:

0.107

Gnomad4 SAS exome

AF:

0.205

Gnomad4 FIN exome

AF:

0.211

Gnomad4 NFE exome

AF:

0.250

Gnomad4 OTH exome

AF:

0.253

GnomAD4 genome

AF:

0.269

AC:

40908

AN:

152040

Hom.:

5799

Cov.:

AF XY:

0.265

AC XY:

19711

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.339

Gnomad4 AMR

AF:

0.253

Gnomad4 ASJ

AF:

0.313

Gnomad4 EAS

AF:

0.0970

Gnomad4 SAS

AF:

0.193

Gnomad4 FIN

AF:

0.214

Gnomad4 NFE

AF:

0.254

Gnomad4 OTH

AF:

0.293

Alfa

AF:

0.269

Hom.:

2546

Bravo

AF:

0.278

Asia WGS

AF:

0.131

AC:

460

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hepatic veno-occlusive disease-immunodeficiency syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 56% of patients studied by a panel of primary immunodeficiencies. Number of patients: 53. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.0

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000022

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over