rs13010639

Variant names:

• chr2-230171029-C-T
• rs13010639
• NM_080424.4:c.1888-268G>A

Variant summary

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

The NM_080424.4(SP110):​c.1888-268G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 539,118 control chromosomes in the GnomAD database, including 3,101 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 0.093 (746 hom., cov: 32)
  • Exomes 𝑓: 0.10 (2355 hom.)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	NM_080424.4	MANE Select	c.1888-268G>A		intron	N/A	NP_536349.3
	SP110	NM_001378442.1		c.1984-268G>A		intron	N/A	NP_001365371.1
	SP110	NM_001378443.1		c.1966-268G>A		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.1888-268G>A		intron	N/A	ENSP00000258381.6
	SP110	ENST00000358662.9	TSL:1	c.1816-268G>A		intron	N/A	ENSP00000351488.4
	SP110	ENST00000897327.1		c.1816-268G>A		intron	N/A	ENSP00000567386.1

Frequencies

GnomAD3 genomes AF: 0.0931 AC: 14174 AN: 152172 Hom.: 746 Cov.: 32

Gnomad AFR AF: 0.0605

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.0983

Gnomad ASJ AF: 0.0999

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0598

Gnomad FIN AF: 0.0865

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0984

GnomAD4 exome AF: 0.103 AC: 39916 AN: 386828 Hom.: 2355 AF XY: 0.101 AC XY: 20738 AN XY: 204504

African (AFR) AF: 0.0642 AC: 722 AN: 11238

American (AMR) AF: 0.0899 AC: 1521 AN: 16926

Ashkenazi Jewish (ASJ) AF: 0.0965 AC: 1145 AN: 11862

East Asian (EAS) AF: 0.000158 AC: 4 AN: 25252

South Asian (SAS) AF: 0.0701 AC: 3010 AN: 42930

European-Finnish (FIN) AF: 0.0979 AC: 2192 AN: 22386

Middle Eastern (MID) AF: 0.114 AC: 192 AN: 1678

European-Non Finnish (NFE) AF: 0.124 AC: 28807 AN: 232228

Other (OTH) AF: 0.104 AC: 2323 AN: 22328

GnomAD4 genome AF: 0.0932 AC: 14187 AN: 152290 Hom.: 746 Cov.: 32 AF XY: 0.0915 AC XY: 6814 AN XY: 74468

African (AFR) AF: 0.0605 AC: 2516 AN: 41554

American (AMR) AF: 0.0982 AC: 1503 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0999 AC: 347 AN: 3472

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5186

South Asian (SAS) AF: 0.0608 AC: 294 AN: 4832

European-Finnish (FIN) AF: 0.0865 AC: 917 AN: 10606

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

European-Non Finnish (NFE) AF: 0.121 AC: 8259 AN: 68016

Other (OTH) AF: 0.0978 AC: 207 AN: 2116

Alfa AF: 0.0992 Hom.: 567

Bravo AF: 0.0922

Asia WGS AF: 0.0310 AC: 107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.9
DANN	Benign	0.76
PhyloP100		0.14
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: rs13010639; hg19: chr2-231035745;