2-230203004-C-G

Position:

• chr2-230203004-C-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP110	NM_080424.4	c.899-276G>C		intron_variant		ENST00000258381.11	NP_536349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11	c.899-276G>C		intron_variant		2	NM_080424.4	ENSP00000258381	P1

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

Gnomad4 AFR exome AF: 0.0585

Gnomad4 AMR exome AF: 0.00371

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0230

Gnomad4 SAS exome AF: 0.00583

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000207

Gnomad4 OTH exome AF: 0.00467

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

Gnomad4 AFR AF: 0.0559

Gnomad4 AMR AF: 0.00602

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0191

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0104

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.1
DANN	Benign	0.77

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: rs2303540; hg19: chr2-231067720;