rs722555

Variant names:

• chr2-230168800-C-T
• rs722555
• NM_080424.4:c.*324G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378442.1(SP110):​c.*324G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 252,654 control chromosomes in the GnomAD database, including 39,484 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 0.57 (24738 hom., cov: 31)
  • Exomes 𝑓: 0.53 (14746 hom.)
• Consequence: SP110 NM_001378442.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• Publications: 12 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378442.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	NM_080424.4	MANE Select	c.*324G>A		3_prime_UTR	Exon 19 of 19	NP_536349.3
	SP110	NM_001378442.1		c.*324G>A		3_prime_UTR	Exon 20 of 20	NP_001365371.1
	SP110	NM_001378443.1		c.*324G>A		3_prime_UTR	Exon 19 of 19	NP_001365372.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	ENST00000258381.11	TSL:2 MANE Select	c.*324G>A		3_prime_UTR	Exon 19 of 19	ENSP00000258381.6
	SP110	ENST00000358662.9	TSL:1	c.*324G>A		3_prime_UTR	Exon 18 of 18	ENSP00000351488.4
	SP110	ENST00000897325.1		c.*324G>A		3_prime_UTR	Exon 17 of 17	ENSP00000567384.1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86433 AN: 151696 Hom.: 24717 Cov.: 31

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.580

GnomAD4 exome AF: 0.533 AC: 53751 AN: 100840 Hom.: 14746 Cov.: 0 AF XY: 0.530 AC XY: 28569 AN XY: 53860

African (AFR) AF: 0.491 AC: 1566 AN: 3188

American (AMR) AF: 0.469 AC: 2273 AN: 4844

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1500 AN: 2766

East Asian (EAS) AF: 0.388 AC: 2428 AN: 6260

South Asian (SAS) AF: 0.496 AC: 7191 AN: 14506

European-Finnish (FIN) AF: 0.523 AC: 2126 AN: 4066

Middle Eastern (MID) AF: 0.561 AC: 222 AN: 396

European-Non Finnish (NFE) AF: 0.564 AC: 33523 AN: 59422

Other (OTH) AF: 0.542 AC: 2922 AN: 5392

GnomAD4 genome AF: 0.570 AC: 86505 AN: 151814 Hom.: 24738 Cov.: 31 AF XY: 0.565 AC XY: 41910 AN XY: 74158

African (AFR) AF: 0.551 AC: 22802 AN: 41374

American (AMR) AF: 0.528 AC: 8044 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2123 AN: 3470

East Asian (EAS) AF: 0.433 AC: 2242 AN: 5172

South Asian (SAS) AF: 0.551 AC: 2655 AN: 4816

European-Finnish (FIN) AF: 0.580 AC: 6081 AN: 10488

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40472 AN: 67942

Other (OTH) AF: 0.583 AC: 1225 AN: 2102

Alfa AF: 0.587 Hom.: 33385

Bravo AF: 0.564

Asia WGS AF: 0.513 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.3
DANN	Benign	0.43
PhyloP100		1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs722555; hg19: chr2-231033516;