rs2114591

Positions:

• chr2-230185853-G-A
• chr2-230185853-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080424.4(SP110):​c.1279+141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 809,788 control chromosomes in the GnomAD database, including 86,721 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 0.46 (16348 hom., cov: 32)
  • Exomes 𝑓: 0.45 (70373 hom.)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP110	NM_080424.4	c.1279+141C>T		intron_variant		ENST00000258381.11	NP_536349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11	c.1279+141C>T		intron_variant		2	NM_080424.4	ENSP00000258381	P1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69493 AN: 151918 Hom.: 16336 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.477

GnomAD4 exome AF: 0.454 AC: 298477 AN: 657752 Hom.: 70373 AF XY: 0.447 AC XY: 158141 AN XY: 353842

Gnomad4 AFR exome AF: 0.444

Gnomad4 AMR exome AF: 0.677

Gnomad4 ASJ exome AF: 0.413

Gnomad4 EAS exome AF: 0.700

Gnomad4 SAS exome AF: 0.396

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.423

Gnomad4 OTH exome AF: 0.446

GnomAD4 genome AF: 0.457 AC: 69529 AN: 152036 Hom.: 16348 Cov.: 32 AF XY: 0.463 AC XY: 34438 AN XY: 74346

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.476

Alfa AF: 0.439 Hom.: 29656

Bravo AF: 0.469

Asia WGS AF: 0.514 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.10
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs2114591; hg19: chr2-231050569; COSMIC: COSV51247288;