chr2-230172900-A-G

Variant names:

• chr2-230172900-A-G
• rs35495464
• NM_080424.4:c.1650T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_080424.4(SP110):​c.1650T>C​(p.Gly550Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0678 in 1,613,902 control chromosomes in the GnomAD database, including 4,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (302 hom., cov: 32)
  • Exomes 𝑓: 0.069 (3957 hom.)
• Consequence: SP110 NM_080424.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.640
• Publications: 5 publications found

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

ENSG00000225963 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-230172900-A-G is Benign according to our data. Variant chr2-230172900-A-G is described in ClinVar as Benign. ClinVar VariationId is 334900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.64 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.078 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080424.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	NM_080424.4	MANE Select	c.1650T>C	p.Gly550Gly	synonymous	Exon 15 of 19	NP_536349.3
	SP110	NM_001378442.1		c.1668T>C	p.Gly556Gly	synonymous	Exon 16 of 20	NP_001365371.1
	SP110	NM_001378443.1		c.1650T>C	p.Gly550Gly	synonymous	Exon 15 of 19	NP_001365372.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	ENST00000258381.11	TSL:2 MANE Select	c.1650T>C	p.Gly550Gly	synonymous	Exon 15 of 19	ENSP00000258381.6
	SP110	ENST00000358662.9	TSL:1	c.1650T>C	p.Gly550Gly	synonymous	Exon 15 of 18	ENSP00000351488.4
	SP110	ENST00000477068.1	TSL:2	n.615T>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0531 AC: 8079 AN: 152144 Hom.: 302 Cov.: 32

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0519

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0545

Gnomad FIN AF: 0.0337

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0798

Gnomad OTH AF: 0.0630

GnomAD2 exomes AF: 0.0599 AC: 15054 AN: 251396 AF XY: 0.0619

Gnomad AFR exome AF: 0.0125

Gnomad AMR exome AF: 0.0357

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.00332

Gnomad FIN exome AF: 0.0316

Gnomad NFE exome AF: 0.0817

Gnomad OTH exome AF: 0.0738

GnomAD4 exome AF: 0.0693 AC: 101303 AN: 1461640 Hom.: 3957 Cov.: 31 AF XY: 0.0694 AC XY: 50456 AN XY: 727142

African (AFR) AF: 0.0124 AC: 414 AN: 33478

American (AMR) AF: 0.0383 AC: 1713 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 3799 AN: 26132

East Asian (EAS) AF: 0.00171 AC: 68 AN: 39690

South Asian (SAS) AF: 0.0526 AC: 4538 AN: 86250

European-Finnish (FIN) AF: 0.0330 AC: 1764 AN: 53416

Middle Eastern (MID) AF: 0.0869 AC: 501 AN: 5764

European-Non Finnish (NFE) AF: 0.0759 AC: 84442 AN: 1111816

Other (OTH) AF: 0.0673 AC: 4064 AN: 60378

GnomAD4 genome AF: 0.0530 AC: 8072 AN: 152262 Hom.: 302 Cov.: 32 AF XY: 0.0507 AC XY: 3772 AN XY: 74440

African (AFR) AF: 0.0129 AC: 536 AN: 41550

American (AMR) AF: 0.0518 AC: 793 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 473 AN: 3470

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5180

South Asian (SAS) AF: 0.0535 AC: 258 AN: 4826

European-Finnish (FIN) AF: 0.0337 AC: 357 AN: 10608

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0798 AC: 5426 AN: 68006

Other (OTH) AF: 0.0624 AC: 132 AN: 2116

Alfa AF: 0.0753 Hom.: 242

Bravo AF: 0.0521

Asia WGS AF: 0.0280 AC: 97 AN: 3478

EpiCase AF: 0.0807

EpiControl AF: 0.0834

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Nov 29, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Hepatic veno-occlusive disease-immunodeficiency syndrome Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.57
DANN	Benign	0.58
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35495464; hg19: chr2-231037616; COSMIC: COSV107250758; COSMIC: COSV107250758;