chr2-230173117-T-C

Variant names:

• chr2-230173117-T-C
• rs10498244
• NM_080424.4:c.1591-158A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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), PanelApp Australia, 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080424.4. 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.1591-158A>G		intron	N/A	NP_536349.3	Q9HB58-6
	SP110	NM_001378442.1		c.1609-158A>G		intron	N/A	NP_001365371.1
	SP110	NM_001378443.1		c.1591-158A>G		intron	N/A	NP_001365372.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	ENST00000258381.11	TSL:2 MANE Select	c.1591-158A>G		intron	N/A	ENSP00000258381.6	Q9HB58-6
	SP110	ENST00000358662.9	TSL:1	c.1591-158A>G		intron	N/A	ENSP00000351488.4	Q9HB58-1
	SP110	ENST00000897327.1		c.1591-158A>G		intron	N/A	ENSP00000567386.1

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

African (AFR) AF: 0.198 AC: 2846 AN: 14358

American (AMR) AF: 0.187 AC: 6097 AN: 32644

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 4669 AN: 17980

East Asian (EAS) AF: 0.165 AC: 4749 AN: 28702

South Asian (SAS) AF: 0.262 AC: 15692 AN: 59866

European-Finnish (FIN) AF: 0.284 AC: 9209 AN: 32398

Middle Eastern (MID) AF: 0.267 AC: 699 AN: 2618

European-Non Finnish (NFE) AF: 0.294 AC: 80717 AN: 274678

Other (OTH) AF: 0.271 AC: 7268 AN: 26814

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

African (AFR) AF: 0.201 AC: 8308 AN: 41424

American (AMR) AF: 0.219 AC: 3344 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 911 AN: 3470

East Asian (EAS) AF: 0.160 AC: 822 AN: 5146

South Asian (SAS) AF: 0.267 AC: 1278 AN: 4790

European-Finnish (FIN) AF: 0.281 AC: 2967 AN: 10562

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20229 AN: 67920

Other (OTH) AF: 0.258 AC: 544 AN: 2108

Alfa AF: 0.280 Hom.: 18771

Bravo AF: 0.248

Asia WGS AF: 0.194 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.5
DANN	Benign	0.63
PhyloP100		-0.087
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: rs10498244; hg19: chr2-231037833; COSMIC: COSV51247364; COSMIC: COSV51247364;