rs41309096

Variant names:

• chr2-230212439-G-A
• rs41309096
• NM_080424.4:c.584-9C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_080424.4(SP110):​c.584-9C>T variant causes a 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 intron
• Scores: Splicing: ADA: 0.00002188
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.176
• Publications: 10 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SP110	NM_080424.4	c.584-9C>T		intron_variant	Intron 4 of 18	ENST00000258381.11	NP_536349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11	c.584-9C>T		intron_variant	Intron 4 of 18	2	NM_080424.4	ENSP00000258381.6

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40875 AN: 151922 Hom.: 5788 Cov.: 32

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

GnomAD2 exomes AF: 0.238 AC: 59759 AN: 250638 AF XY: 0.237

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 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.: 29 AF XY: 0.246 AC XY: 175123 AN XY: 713312

African (AFR) AF: 0.344 AC: 11357 AN: 32994

American (AMR) AF: 0.259 AC: 11578 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 8082 AN: 25916

East Asian (EAS) AF: 0.107 AC: 4256 AN: 39606

South Asian (SAS) AF: 0.205 AC: 17548 AN: 85714

European-Finnish (FIN) AF: 0.211 AC: 11261 AN: 53336

Middle Eastern (MID) AF: 0.314 AC: 1792 AN: 5706

European-Non Finnish (NFE) AF: 0.250 AC: 271006 AN: 1083280

Other (OTH) AF: 0.253 AC: 15015 AN: 59256

GnomAD4 genome AF: 0.269 AC: 40908 AN: 152040 Hom.: 5799 Cov.: 32 AF XY: 0.265 AC XY: 19711 AN XY: 74326

African (AFR) AF: 0.339 AC: 14041 AN: 41436

American (AMR) AF: 0.253 AC: 3867 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1087 AN: 3472

East Asian (EAS) AF: 0.0970 AC: 502 AN: 5174

South Asian (SAS) AF: 0.193 AC: 931 AN: 4824

European-Finnish (FIN) AF: 0.214 AC: 2258 AN: 10566

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17270 AN: 67976

Other (OTH) AF: 0.293 AC: 619 AN: 2114

Alfa AF: 0.263 Hom.: 3347

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

Submissions by phenotype

Hepatic veno-occlusive disease-immunodeficiency syndrome Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.0
DANN	Benign	0.64
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs41309096; hg19: chr2-231077154; COSMIC: COSV51249788; COSMIC: COSV51249788;