2-230172150-G-A

Position:

chr2-230172150-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_080424.4(SP110):c.1731C>T(p.Cys577=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,608,768 control chromosomes in the GnomAD database, including 10,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 847 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10088 hom. )

Consequence

SP110
NM_080424.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.46

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 2-230172150-G-A is Benign according to our data. Variant chr2-230172150-G-A is described in ClinVar as [Benign]. Clinvar id is 334898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-230172150-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 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.1731C>T	p.Cys577=	synonymous_variant	16/19	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.1731C>T	p.Cys577=	synonymous_variant	16/19	2	NM_080424.4	ENSP00000258381	P1	Q9HB58-6
	ENST00000628587.2 linkuse as main transcript	n.1055G>A		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

AF:

0.101

AC:

15400

AN:

152168

Hom.:

846

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0888

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0597

Gnomad FIN

AF:

0.0861

Gnomad MID

AF:

0.137

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.101

GnomAD3 exomes

AF:

0.0949

AC:

23860

AN:

251346

Hom.:

1333

AF XY:

0.0955

AC XY:

12970

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.0853

Gnomad AMR exome

AF:

0.0783

Gnomad ASJ exome

AF:

0.0967

Gnomad EAS exome

AF:

0.000490

Gnomad SAS exome

AF:

0.0690

Gnomad FIN exome

AF:

0.0883

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.0979

GnomAD4 exome

AF:

0.113

AC:

163971

AN:

1456482

Hom.:

10088

Cov.:

AF XY:

0.112

AC XY:

80895

AN XY:

724922

show subpopulations

Gnomad4 AFR exome

AF:

0.0878

Gnomad4 AMR exome

AF:

0.0793

Gnomad4 ASJ exome

AF:

0.0959

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.0700

Gnomad4 FIN exome

AF:

0.0917

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.106

GnomAD4 genome

AF:

0.101

AC:

15419

AN:

152286

Hom.:

847

Cov.:

AF XY:

0.0991

AC XY:

7381

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0890

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.100

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.0605

Gnomad4 FIN

AF:

0.0861

Gnomad4 NFE

AF:

0.121

Gnomad4 OTH

AF:

0.101

Alfa

AF:

0.103

Hom.:

627

Bravo

AF:

0.102

Asia WGS

AF:

0.0320

AC:

113

AN:

3478

EpiCase

AF:

0.118

EpiControl

AF:

0.124

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 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	Feb 01, 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: Frequency -

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

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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