rs11556887

Positions:

chr2-230212961-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.383C>T(p.Ala128Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0965 in 1,613,944 control chromosomes in the GnomAD database, including 9,150 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.077 ( 584 hom., cov: 31)

Exomes 𝑓: 0.099 ( 8566 hom. )

Consequence

SP110
NM_080424.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.128

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 (MetaRNN=0.004897028).

BP6

Variant 2-230212961-G-A is Benign according to our data. Variant chr2-230212961-G-A is described in ClinVar as [Benign]. Clinvar id is 334917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.222 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.383C>T	p.Ala128Val	missense_variant	4/19	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.383C>T	p.Ala128Val	missense_variant	4/19	2	NM_080424.4	ENSP00000258381	P1	Q9HB58-6

Frequencies

GnomAD3 genomes

AF:

0.0768

AC:

11680

AN:

152052

Hom.:

585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0253

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.0588

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.0831

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.0611

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.0981

Gnomad OTH

AF:

0.0810

GnomAD3 exomes

AF:

0.102

AC:

25538

AN:

250300

Hom.:

1819

AF XY:

0.111

AC XY:

15047

AN XY:

135318

show subpopulations

Gnomad AFR exome

AF:

0.0275

Gnomad AMR exome

AF:

0.0411

Gnomad ASJ exome

AF:

0.164

Gnomad EAS exome

AF:

0.0992

Gnomad SAS exome

AF:

0.234

Gnomad FIN exome

AF:

0.0613

Gnomad NFE exome

AF:

0.0983

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.0986

AC:

144096

AN:

1461774

Hom.:

8566

Cov.:

AF XY:

0.104

AC XY:

75459

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.0259

Gnomad4 AMR exome

AF:

0.0451

Gnomad4 ASJ exome

AF:

0.162

Gnomad4 EAS exome

AF:

0.0861

Gnomad4 SAS exome

AF:

0.229

Gnomad4 FIN exome

AF:

0.0626

Gnomad4 NFE exome

AF:

0.0929

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.0767

AC:

11668

AN:

152170

Hom.:

584

Cov.:

AF XY:

0.0780

AC XY:

5805

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0252

Gnomad4 AMR

AF:

0.0587

Gnomad4 ASJ

AF:

0.160

Gnomad4 EAS

AF:

0.0831

Gnomad4 SAS

AF:

0.234

Gnomad4 FIN

AF:

0.0611

Gnomad4 NFE

AF:

0.0981

Gnomad4 OTH

AF:

0.0806

Alfa

AF:

0.0998

Hom.:

1643

Bravo

AF:

0.0706

TwinsUK

AF:

0.0944

AC:

350

ALSPAC

AF:

0.0877

AC:

338

ESP6500AA

AF:

0.0279

AC:

123

ESP6500EA

AF:

0.0936

AC:

805

ExAC

AF:

0.104

AC:

12624

Asia WGS

AF:

0.135

AC:

468

AN:

3478

EpiCase

AF:

0.0985

EpiControl

AF:

0.0985

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hepatic veno-occlusive disease-immunodeficiency syndrome

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

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: MAF -

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

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0045

.;T;T;.;.;T;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.70

T;T;T;T;T;T;T

MetaRNN

Benign

0.0049

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L;.;L;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.7

N;N;N;N;N;N;N

REVEL

Benign

0.062

Sift

Benign

0.060

T;T;D;D;D;D;D

Sift4G

Benign

0.42

T;T;T;T;T;.;D

Polyphen

1.0

D;D;P;.;.;.;.

Vest4

0.11

MPC

0.41

ClinPred

0.011

GERP RS

-1.1

Varity_R

0.026

gMVP

0.44

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