rs13018234

Variant names:

• chr2-230172150-G-A
• rs13018234
• NM_080424.4:c.1731C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-230172150-G-A
• chr2-230172150-G-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.1731C>T​(p.Cys577Cys) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.46
• Publications: 14 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=-0.64).
• BP6: Variant 2-230172150-G-A is Benign according to our data. Variant chr2-230172150-G-A is described in ClinVar as Benign. ClinVar VariationId is 334898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

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.1731C>T	p.Cys577Cys	synonymous	Exon 16 of 19	NP_536349.3
	SP110	NM_001378442.1		c.1749C>T	p.Cys583Cys	synonymous	Exon 17 of 20	NP_001365371.1
	SP110	NM_001378443.1		c.1731C>T	p.Cys577Cys	synonymous	Exon 16 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.1731C>T	p.Cys577Cys	synonymous	Exon 16 of 19	ENSP00000258381.6
	SP110	ENST00000358662.9	TSL:1	c.1731C>T	p.Cys577Cys	synonymous	Exon 16 of 18	ENSP00000351488.4
	ENSG00000225963	ENST00000454058.4	TSL:5	n.1122G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15400 AN: 152168 Hom.: 846 Cov.: 33

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

GnomAD2 exomes AF: 0.0949 AC: 23860 AN: 251346 AF XY: 0.0955

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 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.: 30 AF XY: 0.112 AC XY: 80895 AN XY: 724922

African (AFR) AF: 0.0878 AC: 2929 AN: 33364

American (AMR) AF: 0.0793 AC: 3548 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0959 AC: 2506 AN: 26118

East Asian (EAS) AF: 0.000378 AC: 15 AN: 39682

South Asian (SAS) AF: 0.0700 AC: 6031 AN: 86210

European-Finnish (FIN) AF: 0.0917 AC: 4897 AN: 53388

Middle Eastern (MID) AF: 0.114 AC: 659 AN: 5760

European-Non Finnish (NFE) AF: 0.124 AC: 136977 AN: 1107000

Other (OTH) AF: 0.106 AC: 6409 AN: 60240

GnomAD4 genome AF: 0.101 AC: 15419 AN: 152286 Hom.: 847 Cov.: 33 AF XY: 0.0991 AC XY: 7381 AN XY: 74476

African (AFR) AF: 0.0890 AC: 3696 AN: 41544

American (AMR) AF: 0.101 AC: 1548 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 347 AN: 3468

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5184

South Asian (SAS) AF: 0.0605 AC: 292 AN: 4824

European-Finnish (FIN) AF: 0.0861 AC: 914 AN: 10618

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.121 AC: 8263 AN: 68022

Other (OTH) AF: 0.101 AC: 213 AN: 2112

Alfa AF: 0.104 Hom.: 881

Bravo AF: 0.102

Asia WGS AF: 0.0320 AC: 113 AN: 3478

EpiCase AF: 0.118

EpiControl AF: 0.124

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hepatic veno-occlusive disease-immunodeficiency syndrome (2)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.67
PhyloP100		2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13018234; hg19: chr2-231036866;