rs10208770

Variant names:

• chr2-230170151-T-G
• rs10208770
• NM_080424.4:c.2028+470A>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.2028+470A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,216 control chromosomes in the GnomAD database, including 1,861 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 0.14 (1861 hom., cov: 32)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 6 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]

SP110 Gene-Disease associations (from GenCC):

• hepatic veno-occlusive disease-immunodeficiency syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Ambry Genetics

ENSG00000225963 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4	c.2028+470A>C		intron_variant	Intron 18 of 18	ENST00000258381.11	NP_536349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11	c.2028+470A>C		intron_variant	Intron 18 of 18	2	NM_080424.4	ENSP00000258381.6

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21852 AN: 152098 Hom.: 1848 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0727

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.144 AC: 21896 AN: 152216 Hom.: 1861 Cov.: 32 AF XY: 0.143 AC XY: 10615 AN XY: 74430

African (AFR) AF: 0.226 AC: 9377 AN: 41514

American (AMR) AF: 0.124 AC: 1890 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 369 AN: 3468

East Asian (EAS) AF: 0.129 AC: 669 AN: 5184

South Asian (SAS) AF: 0.166 AC: 802 AN: 4822

European-Finnish (FIN) AF: 0.0727 AC: 772 AN: 10618

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7534 AN: 67994

Other (OTH) AF: 0.146 AC: 309 AN: 2112

Alfa AF: 0.121 Hom.: 2326

Bravo AF: 0.149

Asia WGS AF: 0.137 AC: 479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.51
DANN	Benign	0.70
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs10208770; hg19: chr2-231034867;