rs1004869

chr2-230174555-C-A

Variant summary

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

The NM_080424.4(SP110):c.1591-1596G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 151,884 control chromosomes in the GnomAD database, including 990 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 0.11 (990 hom., cov: 32)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SP110	NM_080424.4	c.1591-1596G>T		intron_variant		ENST00000258381.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SP110	ENST00000258381.11	c.1591-1596G>T		intron_variant		2	NM_080424.4	P1
SP110	ENST00000358662.9	c.1591-1596G>T		intron_variant		1
SP110	ENST00000698099.1	c.1591-1596G>T		intron_variant, NMD_transcript_variant
SP110	ENST00000698100.1	c.1441-1596G>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16819 AN: 151766 Hom.: 989 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0619

Gnomad FIN AF: 0.0836

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.111 AC: 16841 AN: 151884 Hom.: 990 Cov.: 32 AF XY: 0.109 AC XY: 8073 AN XY: 74250

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0628

Gnomad4 FIN AF: 0.0836

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.108

Alfa AF: 0.116 Hom.: 523

Bravo AF: 0.114

Asia WGS AF: 0.0370 AC: 130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.51
Dann	Benign	0.22

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: rs1004869; hg19: chr2-231039271;