chr2-230211574-T-G

Variant names:

Variant summary

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

The NM_080424.4(SP110):c.668-21A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,472,124 control chromosomes in the GnomAD database, including 157,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 18682 hom., cov: 30)

Exomes 𝑓: 0.45 ( 138527 hom. )

Consequence

SP110
NM_080424.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.53

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=-0.7).

BP6

Variant 2-230211574-T-G is Benign according to our data. Variant chr2-230211574-T-G is described in ClinVar as [Benign]. Clinvar id is 1333151.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4 link	c.668-21A>C		intron_variant	Intron 5 of 18	ENST00000258381.11	NP_536349.3	Q9HB58-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11 link	c.668-21A>C		intron_variant	Intron 5 of 18	2	NM_080424.4	ENSP00000258381.6		Q9HB58-6

Frequencies

GnomAD3 genomes

AF:

0.489

AC:

74070

AN:

151570

Hom.:

18658

Cov.:

show subpopulations

Gnomad AFR

AF:

0.543

Gnomad AMI

AF:

0.429

Gnomad AMR

AF:

0.606

Gnomad ASJ

AF:

0.422

Gnomad EAS

AF:

0.707

Gnomad SAS

AF:

0.416

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.497

GnomAD3 exomes

AF:

0.490

AC:

122953

AN:

250776

Hom.:

31800

AF XY:

0.476

AC XY:

64496

AN XY:

135526

show subpopulations

Gnomad AFR exome

AF:

0.548

Gnomad AMR exome

AF:

0.697

Gnomad ASJ exome

AF:

0.406

Gnomad EAS exome

AF:

0.697

Gnomad SAS exome

AF:

0.413

Gnomad FIN exome

AF:

0.445

Gnomad NFE exome

AF:

0.424

Gnomad OTH exome

AF:

0.471

GnomAD4 exome

AF:

0.454

AC:

600072

AN:

1320436

Hom.:

138527

Cov.:

AF XY:

0.450

AC XY:

299264

AN XY:

664356

show subpopulations

Gnomad4 AFR exome

AF:

0.551

Gnomad4 AMR exome

AF:

0.683

Gnomad4 ASJ exome

AF:

0.417

Gnomad4 EAS exome

AF:

0.697

Gnomad4 SAS exome

AF:

0.419

Gnomad4 FIN exome

AF:

0.441

Gnomad4 NFE exome

AF:

0.436

Gnomad4 OTH exome

AF:

0.460

GnomAD4 genome

AF:

0.489

AC:

74136

AN:

151688

Hom.:

18682

Cov.:

AF XY:

0.494

AC XY:

36624

AN XY:

74080

show subpopulations

Gnomad4 AFR

AF:

0.542

Gnomad4 AMR

AF:

0.607

Gnomad4 ASJ

AF:

0.422

Gnomad4 EAS

AF:

0.706

Gnomad4 SAS

AF:

0.416

Gnomad4 FIN

AF:

0.458

Gnomad4 NFE

AF:

0.427

Gnomad4 OTH

AF:

0.497

Alfa

AF:

0.445

Hom.:

4964

Bravo

AF:

0.505

Asia WGS

AF:

0.531

AC:

1848

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

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 88% of patients studied by a panel of primary immunodeficiencies. Number of patients: 84. Only high quality variants are reported. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hepatic veno-occlusive disease-immunodeficiency syndrome

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.88

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

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