rs28930679

Positions:

Variant summary

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

The NM_080424.4(SP110):c.617C>T(p.Ala206Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,606,272 control chromosomes in the GnomAD database, including 44,658 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3464 hom., cov: 32)

Exomes 𝑓: 0.23 ( 41194 hom. )

Consequence

SP110
NM_080424.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.0930

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=0.010025024).

BP6

Variant 2-230212397-G-A is Benign according to our data. Variant chr2-230212397-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 334911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-230212397-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP110	NM_080424.4 link	c.617C>T	p.Ala206Val	missense_variant	5/19	ENST00000258381.11	NP_536349.3	Q9HB58-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11 link	c.617C>T	p.Ala206Val	missense_variant	5/19	2	NM_080424.4	ENSP00000258381.6		Q9HB58-6

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

31231

AN:

151984

Hom.:

3464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.0972

Gnomad SAS

AF:

0.166

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.282

Gnomad NFE

AF:

0.245

Gnomad OTH

AF:

0.237

GnomAD3 exomes

AF:

0.214

AC:

53736

AN:

250976

Hom.:

6019

AF XY:

0.215

AC XY:

29204

AN XY:

135626

show subpopulations

Gnomad AFR exome

AF:

0.144

Gnomad AMR exome

AF:

0.244

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.0847

Gnomad SAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.203

Gnomad NFE exome

AF:

0.241

Gnomad OTH exome

AF:

0.238

GnomAD4 exome

AF:

0.234

AC:

340263

AN:

1454170

Hom.:

41194

Cov.:

AF XY:

0.233

AC XY:

168649

AN XY:

723754

show subpopulations

Gnomad4 AFR exome

AF:

0.144

Gnomad4 AMR exome

AF:

0.243

Gnomad4 ASJ exome

AF:

0.286

Gnomad4 EAS exome

AF:

0.107

Gnomad4 SAS exome

AF:

0.180

Gnomad4 FIN exome

AF:

0.207

Gnomad4 NFE exome

AF:

0.245

Gnomad4 OTH exome

AF:

0.231

GnomAD4 genome

AF:

0.205

AC:

31238

AN:

152102

Hom.:

3464

Cov.:

AF XY:

0.203

AC XY:

15126

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.220

Gnomad4 ASJ

AF:

0.286

Gnomad4 EAS

AF:

0.0967

Gnomad4 SAS

AF:

0.166

Gnomad4 FIN

AF:

0.211

Gnomad4 NFE

AF:

0.245

Gnomad4 OTH

AF:

0.233

Alfa

AF:

0.234

Hom.:

6038

Bravo

AF:

0.206

TwinsUK

AF:

0.243

AC:

901

ALSPAC

AF:

0.257

AC:

992

ESP6500AA

AF:

0.141

AC:

623

ESP6500EA

AF:

0.253

AC:

2177

ExAC

AF:

0.211

AC:

25613

Asia WGS

AF:

0.107

AC:

375

AN:

3478

EpiCase

AF:

0.259

EpiControl

AF:

0.258

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hepatic veno-occlusive disease-immunodeficiency syndrome

Benign:4

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:3

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: Frequency -
Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 03, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 52% of patients studied by a panel of primary immunodeficiencies. Number of patients: 49. Only high quality variants are reported. -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 23, 2019	This variant is associated with the following publications: (PMID: 30697212) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.7

DANN

Benign

0.89

DEOGEN2

Benign

0.0019

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

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.63

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

MetaRNN

Benign

0.0046

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

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

N;N;.;N;.;.;.

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.43

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

REVEL

Benign

0.043

Sift

Benign

0.050

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

Sift4G

Benign

0.28

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

Polyphen

0.0010

B;B;B;.;.;.;.

Vest4

0.051

MPC

0.13

ClinPred

0.00012

GERP RS

-0.15

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.022

gMVP

0.11

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