Genetic Variant SP110:c.1279+141C>T (chr2-230185853-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_080424.4(SP110):c.1279+141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 809,788 control chromosomes in the GnomAD database, including 86,721 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 0.46 ( 16348 hom., cov: 32)

Exomes 𝑓: 0.45 ( 70373 hom. )

Consequence

SP110
NM_080424.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.73

Publications

11 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 Gene-Disease associations (from GenCC):

hepatic veno-occlusive disease-immunodeficiency syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Ambry Genetics

SP110 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4 link	c.1279+141C>T		intron_variant	Intron 11 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.1279+141C>T		intron_variant	Intron 11 of 18	2	NM_080424.4	ENSP00000258381.6		Q9HB58-6

Frequencies

GnomAD3 genomes

AF:

0.457

AC:

69493

AN:

151918

Hom.:

16336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.429

Gnomad AMR

AF:

0.591

Gnomad ASJ

AF:

0.420

Gnomad EAS

AF:

0.693

Gnomad SAS

AF:

0.390

Gnomad FIN

AF:

0.456

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.477

GnomAD4 exome

AF:

0.454

AC:

298477

AN:

657752

Hom.:

70373

AF XY:

0.447

AC XY:

158141

AN XY:

353842

show subpopulations

African (AFR)

AF:

0.444

AC:

8055

AN:

18128

American (AMR)

AF:

0.677

AC:

28156

AN:

41600

Ashkenazi Jewish (ASJ)

AF:

0.413

AC:

8366

AN:

20236

East Asian (EAS)

AF:

0.700

AC:

24880

AN:

35542

South Asian (SAS)

AF:

0.396

AC:

26671

AN:

67416

European-Finnish (FIN)

AF:

0.438

AC:

20826

AN:

47544

Middle Eastern (MID)

AF:

0.427

AC:

1671

AN:

3914

European-Non Finnish (NFE)

AF:

0.423

AC:

164763

AN:

389568

Other (OTH)

AF:

0.446

AC:

15089

AN:

33804

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

8121

16241

24362

32482

40603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1974

3948

5922

7896

9870

<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:

0.457

AC:

69529

AN:

152036

Hom.:

16348

Cov.:

AF XY:

0.463

AC XY:

34438

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.446

AC:

18482

AN:

41470

American (AMR)

AF:

0.591

AC:

9034

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.420

AC:

1457

AN:

3468

East Asian (EAS)

AF:

0.693

AC:

3582

AN:

5172

South Asian (SAS)

AF:

0.389

AC:

1876

AN:

4820

European-Finnish (FIN)

AF:

0.456

AC:

4814

AN:

10560

Middle Eastern (MID)

AF:

0.476

AC:

139

AN:

292

European-Non Finnish (NFE)

AF:

0.423

AC:

28746

AN:

67946

Other (OTH)

AF:

0.476

AC:

1008

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1920

3840

5761

7681

9601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<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:

0.442

Hom.:

44815

Bravo

AF:

0.469

Asia WGS

AF:

0.514

AC:

1787

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.10

(source)

DANN

Benign

0.76

PhyloP100

-2.7

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

Computational scores

Splicing

Publications

Other links and lift over