rs958978

Variant names:

• chr2-230185270-G-A
• rs958978
• NM_080424.4:c.1279+724C>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.1279+724C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 152,102 control chromosomes in the GnomAD database, including 44,472 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 0.76 (44472 hom., cov: 31)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4	c.1279+724C>T		intron_variant	Intron 11 of 18	ENST00000258381.11	NP_536349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11	c.1279+724C>T		intron_variant	Intron 11 of 18	2	NM_080424.4	ENSP00000258381.6

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116069 AN: 151984 Hom.: 44447 Cov.: 31

Gnomad AFR AF: 0.721

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.764 AC: 116140 AN: 152102 Hom.: 44472 Cov.: 31 AF XY: 0.765 AC XY: 56873 AN XY: 74366

African (AFR) AF: 0.720 AC: 29844 AN: 41440

American (AMR) AF: 0.826 AC: 12620 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2568 AN: 3470

East Asian (EAS) AF: 0.816 AC: 4218 AN: 5172

South Asian (SAS) AF: 0.677 AC: 3259 AN: 4814

European-Finnish (FIN) AF: 0.803 AC: 8508 AN: 10596

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52571 AN: 68012

Other (OTH) AF: 0.763 AC: 1611 AN: 2112

Alfa AF: 0.752 Hom.: 6141

Bravo AF: 0.766

Asia WGS AF: 0.747 AC: 2597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.2
DANN	Benign	0.78
PhyloP100		0.23
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: rs958978; hg19: chr2-231049986; COSMIC: COSV51255398;