2-230173117-T-C

Variant summary

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

The NM_080424.4(SP110):c.1591-158A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 641,962 control chromosomes in the GnomAD database, including 23,651 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 0.26 (5160 hom., cov: 31)
  • Exomes 𝑓: 0.27 (18491 hom.)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SP110	NM_080424.4	c.1591-158A>G		intron_variant		ENST00000258381.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SP110	ENST00000258381.11	c.1591-158A>G		intron_variant		2	NM_080424.4	P1
	ENST00000628587.2	n.1099-571T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38831 AN: 151786 Hom.: 5165 Cov.: 31

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.269 AC: 131946 AN: 490058 Hom.: 18491 Cov.: 4 AF XY: 0.270 AC XY: 70859 AN XY: 262554

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.262

Gnomad4 FIN exome AF: 0.284

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.271

GnomAD4 genome AF: 0.256 AC: 38834 AN: 151904 Hom.: 5160 Cov.: 31 AF XY: 0.252 AC XY: 18678 AN XY: 74232

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.258

Alfa AF: 0.286 Hom.: 12727

Bravo AF: 0.248

Asia WGS AF: 0.194 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	7.5
Dann	Benign	0.63

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: rs10498244; hg19: chr2-231037833; COSMIC: COSV51247364; COSMIC: COSV51247364;