rs1004869

Variant names:

• chr2-230174555-C-A
• rs1004869
• NM_080424.4:c.1591-1596G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080424.4(SP110):​c.1591-1596G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 151,884 control chromosomes in the GnomAD database, including 990 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (990 hom., cov: 32)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 4 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), PanelApp Australia, Orphanet, ClinGen, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	NM_080424.4	MANE Select	c.1591-1596G>T		intron	N/A	NP_536349.3	Q9HB58-6
	SP110	NM_001378442.1		c.1609-1596G>T		intron	N/A	NP_001365371.1
	SP110	NM_001378443.1		c.1591-1596G>T		intron	N/A	NP_001365372.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	ENST00000258381.11	TSL:2 MANE Select	c.1591-1596G>T		intron	N/A	ENSP00000258381.6	Q9HB58-6
	SP110	ENST00000358662.9	TSL:1	c.1591-1596G>T		intron	N/A	ENSP00000351488.4	Q9HB58-1
	SP110	ENST00000897327.1		c.1591-1596G>T		intron	N/A	ENSP00000567386.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16819 AN: 151766 Hom.: 989 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0619

Gnomad FIN AF: 0.0836

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.109

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.111 AC: 16841 AN: 151884 Hom.: 990 Cov.: 32 AF XY: 0.109 AC XY: 8073 AN XY: 74250

African (AFR) AF: 0.124 AC: 5145 AN: 41392

American (AMR) AF: 0.104 AC: 1591 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3472

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

South Asian (SAS) AF: 0.0628 AC: 303 AN: 4824

European-Finnish (FIN) AF: 0.0836 AC: 881 AN: 10534

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8191 AN: 67894

Other (OTH) AF: 0.108 AC: 229 AN: 2112

Alfa AF: 0.118 Hom.: 699

Bravo AF: 0.114

Asia WGS AF: 0.0370 AC: 130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.51
DANN	Benign	0.22
PhyloP100		0.0
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: rs1004869; hg19: chr2-231039271;