NM_080424.4:c.899-276G>C

Variant names:

• chr2-230203004-C-G
• rs2303540
• NM_080424.4:c.899-276G>C

Variant summary

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

The NM_080424.4(SP110):​c.899-276G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00847 in 470,592 control chromosomes in the GnomAD database, including 79 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 0.017 (51 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (28 hom.)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.327
• 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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.054 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.899-276G>C		intron	N/A	NP_536349.3	Q9HB58-6
	SP110	NM_001378442.1		c.917-276G>C		intron	N/A	NP_001365371.1
	SP110	NM_001378443.1		c.899-276G>C		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.899-276G>C		intron	N/A	ENSP00000258381.6	Q9HB58-6
	SP110	ENST00000358662.9	TSL:1	c.899-276G>C		intron	N/A	ENSP00000351488.4	Q9HB58-1
	SP110	ENST00000258382.10	TSL:1	c.899-276G>C		intron	N/A	ENSP00000258382.5	Q9HB58-3

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2549 AN: 152090 Hom.: 47 Cov.: 32

Gnomad AFR AF: 0.0555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00603

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0193

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00444 AC: 1414 AN: 318384 Hom.: 28 Cov.: 0 AF XY: 0.00431 AC XY: 731 AN XY: 169468

African (AFR) AF: 0.0585 AC: 551 AN: 9418

American (AMR) AF: 0.00371 AC: 52 AN: 14008

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9492

East Asian (EAS) AF: 0.0230 AC: 443 AN: 19278

South Asian (SAS) AF: 0.00583 AC: 244 AN: 41882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16420

Middle Eastern (MID) AF: 0.000732 AC: 1 AN: 1366

European-Non Finnish (NFE) AF: 0.000207 AC: 39 AN: 188520

Other (OTH) AF: 0.00467 AC: 84 AN: 18000

GnomAD4 genome AF: 0.0169 AC: 2570 AN: 152208 Hom.: 51 Cov.: 32 AF XY: 0.0164 AC XY: 1220 AN XY: 74418

African (AFR) AF: 0.0559 AC: 2320 AN: 41522

American (AMR) AF: 0.00602 AC: 92 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0191 AC: 99 AN: 5178

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68008

Other (OTH) AF: 0.0104 AC: 22 AN: 2110

Alfa AF: 0.0127 Hom.: 3

Bravo AF: 0.0196

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.1
DANN	Benign	0.77
PhyloP100		0.33
PromoterAI		-0.16	Neutral
Mutation Taster		=100/0	polymorphism

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: rs2303540; hg19: chr2-231067720;