2-230211574-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

10 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

GnomAD2 exomes

AF:

0.490

AC:

122953

AN:

250776

AF XY:

0.476

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 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

African (AFR)

AF:

0.551

AC:

17006

AN:

30846

American (AMR)

AF:

0.683

AC:

30421

AN:

44532

Ashkenazi Jewish (ASJ)

AF:

0.417

AC:

10524

AN:

25258

East Asian (EAS)

AF:

0.697

AC:

27262

AN:

39112

South Asian (SAS)

AF:

0.419

AC:

34934

AN:

83344

European-Finnish (FIN)

AF:

0.441

AC:

23480

AN:

53274

Middle Eastern (MID)

AF:

0.442

AC:

2448

AN:

5542

European-Non Finnish (NFE)

AF:

0.436

AC:

428368

AN:

982824

Other (OTH)

AF:

0.460

AC:

25629

AN:

55704

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

15066

30132

45198

60264

75330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12748

25496

38244

50992

63740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.489

AC:

74136

AN:

151688

Hom.:

18682

Cov.:

AF XY:

0.494

AC XY:

36624

AN XY:

74080

show subpopulations

African (AFR)

AF:

0.542

AC:

22415

AN:

41318

American (AMR)

AF:

0.607

AC:

9264

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.422

AC:

1463

AN:

3468

East Asian (EAS)

AF:

0.706

AC:

3636

AN:

5150

South Asian (SAS)

AF:

0.416

AC:

1999

AN:

4804

European-Finnish (FIN)

AF:

0.458

AC:

4807

AN:

10486

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.427

AC:

28975

AN:

67904

Other (OTH)

AF:

0.497

AC:

1045

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1898

3797

5695

7594

9492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.457

Hom.:

7936

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

(source)

DANN

Benign

0.88

PhyloP100

2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over