NM_001378442.1:c.-64+307A>G

Variant names:

• chr2-230225228-T-C
• rs10209615
• ENST00000881924.1:c.-251-366T>C

Variant summary

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

The NM_001378442.1(SP110):​c.-64+307A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,238 control chromosomes in the GnomAD database, including 1,529 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 0.13 (1529 hom., cov: 32)
• Consequence: SP110 NM_001378442.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310
• Publications: 12 publications found

Genes affected

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]

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378442.1. 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_001378442.1		c.-64+307A>G		intron	N/A	NP_001365371.1
	SP110	NM_001378444.1		c.-64+307A>G		intron	N/A	NP_001365373.1
	SP110	NM_001378445.1		c.-64+307A>G		intron	N/A	NP_001365374.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP140	ENST00000881924.1		c.-251-366T>C		intron	N/A	ENSP00000551983.1
	SP110	ENST00000540870.5	TSL:2	c.-64+307A>G		intron	N/A	ENSP00000439558.1	Q9HB58-7
	SP140	ENST00000456542.5	TSL:4	c.-90-527T>C		intron	N/A	ENSP00000475284.1	U3KPV9

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20413 AN: 152120 Hom.: 1528 Cov.: 32

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.134 AC: 20410 AN: 152238 Hom.: 1529 Cov.: 32 AF XY: 0.130 AC XY: 9642 AN XY: 74450

African (AFR) AF: 0.0897 AC: 3725 AN: 41536

American (AMR) AF: 0.122 AC: 1870 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 582 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.144 AC: 694 AN: 4824

European-Finnish (FIN) AF: 0.102 AC: 1080 AN: 10616

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12006 AN: 67990

Other (OTH) AF: 0.135 AC: 285 AN: 2110

Alfa AF: 0.162 Hom.: 5739

Bravo AF: 0.131

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.5
DANN	Benign	0.75
PhyloP100		0.31
PromoterAI		0.027	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10209615; hg19: chr2-231089943;