rs11678451

Variant names:

• chr2-230179651-T-C
• rs11678451
• NM_080424.4:c.1349-1396A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-230179651-T-C
• chr2-230179651-T-G

Variant summary

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

The NM_080424.4(SP110):​c.1349-1396A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,564 control chromosomes in the GnomAD database, including 14,824 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 0.43 (14824 hom., cov: 29)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 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.1349-1396A>G		intron	N/A	NP_536349.3	Q9HB58-6
	SP110	NM_001378442.1		c.1367-1396A>G		intron	N/A	NP_001365371.1
	SP110	NM_001378443.1		c.1349-1396A>G		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.1349-1396A>G		intron	N/A	ENSP00000258381.6	Q9HB58-6
	SP110	ENST00000358662.9	TSL:1	c.1349-1396A>G		intron	N/A	ENSP00000351488.4	Q9HB58-1
	SP110	ENST00000258382.10	TSL:1	c.1349-1396A>G		intron	N/A	ENSP00000258382.5	Q9HB58-3

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65758 AN: 151446 Hom.: 14795 Cov.: 29

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.434 AC: 65819 AN: 151564 Hom.: 14824 Cov.: 29 AF XY: 0.428 AC XY: 31726 AN XY: 74046

African (AFR) AF: 0.517 AC: 21352 AN: 41284

American (AMR) AF: 0.319 AC: 4862 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1639 AN: 3466

East Asian (EAS) AF: 0.128 AC: 658 AN: 5150

South Asian (SAS) AF: 0.370 AC: 1777 AN: 4802

European-Finnish (FIN) AF: 0.415 AC: 4341 AN: 10470

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29799 AN: 67858

Other (OTH) AF: 0.414 AC: 871 AN: 2102

Alfa AF: 0.430 Hom.: 18264

Bravo AF: 0.430

Asia WGS AF: 0.280 AC: 974 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.65
PhyloP100		-1.5
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: rs11678451; hg19: chr2-231044367;