NM_080424.4:c.1349-1493A>G

Variant names:

• chr2-230179748-T-C
• rs919178
• NM_080424.4:c.1349-1493A>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.1349-1493A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,188 control chromosomes in the GnomAD database, including 15,296 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 0.44 (15296 hom., cov: 28)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 2 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4	c.1349-1493A>G		intron_variant	Intron 12 of 18	ENST00000258381.11	NP_536349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11	c.1349-1493A>G		intron_variant	Intron 12 of 18	2	NM_080424.4	ENSP00000258381.6

Frequencies

GnomAD3 genomes AF: 0.442 AC: 66795 AN: 151072 Hom.: 15286 Cov.: 28

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.442 AC: 66832 AN: 151188 Hom.: 15296 Cov.: 28 AF XY: 0.440 AC XY: 32487 AN XY: 73828

African (AFR) AF: 0.573 AC: 23561 AN: 41138

American (AMR) AF: 0.431 AC: 6540 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1402 AN: 3462

East Asian (EAS) AF: 0.337 AC: 1723 AN: 5114

South Asian (SAS) AF: 0.326 AC: 1561 AN: 4784

European-Finnish (FIN) AF: 0.396 AC: 4123 AN: 10422

Middle Eastern (MID) AF: 0.472 AC: 135 AN: 286

European-Non Finnish (NFE) AF: 0.390 AC: 26432 AN: 67808

Other (OTH) AF: 0.447 AC: 936 AN: 2094

Alfa AF: 0.412 Hom.: 16738

Bravo AF: 0.450

Asia WGS AF: 0.360 AC: 1255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.5
DANN	Benign	0.75
PhyloP100		0.047
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: rs919178; hg19: chr2-231044464;