rs41309088

Positions:

chr2-230212968-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_080424.4(SP110):c.376G>A(p.Gly126Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,613,966 control chromosomes in the GnomAD database, including 315 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 Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 44 hom., cov: 31)

Exomes 𝑓: 0.015 ( 271 hom. )

Consequence

SP110
NM_080424.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.240

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=0.0027492046).

BP6

Variant 2-230212968-C-T is Benign according to our data. Variant chr2-230212968-C-T is described in ClinVar as [Benign]. Clinvar id is 334918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-230212968-C-T is described in Lovd as [Benign]. Variant chr2-230212968-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0144 (2188/152142) while in subpopulation NFE AF= 0.0171 (1165/67990). AF 95% confidence interval is 0.0163. There are 44 homozygotes in gnomad4. There are 1172 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP110	NM_080424.4 link	c.376G>A	p.Gly126Ser	missense_variant	4/19	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.376G>A	p.Gly126Ser	missense_variant	4/19	2	NM_080424.4	ENSP00000258381.6		Q9HB58-6

Frequencies

GnomAD3 genomes

AF:

0.0144

AC:

2188

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00643

Gnomad FIN

AF:

0.0589

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0171

Gnomad OTH

AF:

0.0135

GnomAD3 exomes

AF:

0.0163

AC:

4084

AN:

250082

Hom.:

AF XY:

0.0165

AC XY:

2227

AN XY:

135214

show subpopulations

Gnomad AFR exome

AF:

0.00215

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.0195

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00582

Gnomad FIN exome

AF:

0.0579

Gnomad NFE exome

AF:

0.0172

Gnomad OTH exome

AF:

0.0209

GnomAD4 exome

AF:

0.0153

AC:

22418

AN:

1461824

Hom.:

271

Cov.:

AF XY:

0.0152

AC XY:

11046

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.0103

Gnomad4 ASJ exome

AF:

0.0210

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00580

Gnomad4 FIN exome

AF:

0.0548

Gnomad4 NFE exome

AF:

0.0153

Gnomad4 OTH exome

AF:

0.0145

GnomAD4 genome

AF:

0.0144

AC:

2188

AN:

152142

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1172

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00190

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00664

Gnomad4 FIN

AF:

0.0589

Gnomad4 NFE

AF:

0.0171

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0154

Hom.:

Bravo

AF:

0.00975

TwinsUK

AF:

0.0200

AC:

ALSPAC

AF:

0.0179

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0170

AC:

146

ExAC

AF:

0.0154

AC:

1874

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0175

EpiControl

AF:

0.0210

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 12, 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 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

0.084

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.66

CADD

Benign

4.9

DANN

Benign

0.65

DEOGEN2

Benign

0.0012

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

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.66

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

MetaRNN

Benign

0.0027

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

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.34

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

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.57

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

REVEL

Benign

0.044

Sift

Benign

0.097

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

Sift4G

Benign

0.37

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

Polyphen

0.037

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

Vest4

0.099

MPC

0.56

ClinPred

0.0071

GERP RS

0.90

Varity_R

0.024

gMVP

0.22

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