chr2-230210491-G-A

Variant names:

• chr2-230210491-G-A
• rs2114592
• NM_080424.4:c.752-483C>T

Variant summary

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

The NM_080424.4(SP110):​c.752-483C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,214 control chromosomes in the GnomAD database, including 1,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: 𝑓 0.13 (1372 hom., cov: 32)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -1.21
• Publications: 9 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]

SP140 (HGNC:17133): (SP140 nuclear body protein) This gene encodes a member of the SP100 family of proteins, which are share common domains including an N-terminal homogeneously staining region domain followed by a SP100/autoimmune regulator/NucP41/P75/deformed epidermal autoregulatory factor domain, a plant homeobox zinc finger, and a bromodomain. The encoded protein is interferon-inducible and is expressed at high levels in the nuclei of leukocytes. Variants of this gene have been associated with multiple sclerosis, Crohn's disease, and chronic lymphocytic leukemia. Alternative splicing results in multiple variants. [provided by RefSeq, Aug 2016]

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 (SAS) allele frequency at 95% confidence interval = 0.258 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.752-483C>T		intron	N/A	NP_536349.3	Q9HB58-6
	SP110	NM_001378442.1		c.770-483C>T		intron	N/A	NP_001365371.1
	SP110	NM_001378443.1		c.752-483C>T		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.752-483C>T		intron	N/A	ENSP00000258381.6	Q9HB58-6
	SP110	ENST00000358662.9	TSL:1	c.752-483C>T		intron	N/A	ENSP00000351488.4	Q9HB58-1
	SP110	ENST00000258382.10	TSL:1	c.752-483C>T		intron	N/A	ENSP00000258382.5	Q9HB58-3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19169 AN: 152096 Hom.: 1367 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0826

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.0628

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.126 AC: 19191 AN: 152214 Hom.: 1372 Cov.: 32 AF XY: 0.126 AC XY: 9382 AN XY: 74410

African (AFR) AF: 0.169 AC: 7033 AN: 41498

American (AMR) AF: 0.0825 AC: 1263 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 643 AN: 3472

East Asian (EAS) AF: 0.182 AC: 942 AN: 5178

South Asian (SAS) AF: 0.270 AC: 1303 AN: 4824

European-Finnish (FIN) AF: 0.0628 AC: 666 AN: 10612

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6948 AN: 68012

Other (OTH) AF: 0.125 AC: 263 AN: 2110

Alfa AF: 0.120 Hom.: 690

Bravo AF: 0.126

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Mycobacterium tuberculosis, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.37
PhyloP100		-1.2
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: rs2114592; hg19: chr2-231075206;