2-230196476-C-T

Variant names:

• chr2-230196476-C-T
• rs1469345
• NM_080424.4:c.1129+4409G>A

Variant summary

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

The NM_080424.4(SP110):​c.1129+4409G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 151,896 control chromosomes in the GnomAD database, including 44,488 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 0.76 (44488 hom., cov: 31)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 0 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4	c.1129+4409G>A		intron_variant	Intron 10 of 18	ENST00000258381.11	NP_536349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11	c.1129+4409G>A		intron_variant	Intron 10 of 18	2	NM_080424.4	ENSP00000258381.6

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116017 AN: 151778 Hom.: 44463 Cov.: 31

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.737

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.764 AC: 116088 AN: 151896 Hom.: 44488 Cov.: 31 AF XY: 0.765 AC XY: 56813 AN XY: 74222

African (AFR) AF: 0.723 AC: 29978 AN: 41440

American (AMR) AF: 0.826 AC: 12607 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.737 AC: 2556 AN: 3470

East Asian (EAS) AF: 0.815 AC: 4228 AN: 5186

South Asian (SAS) AF: 0.677 AC: 3263 AN: 4822

European-Finnish (FIN) AF: 0.803 AC: 8385 AN: 10444

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52523 AN: 67958

Other (OTH) AF: 0.762 AC: 1607 AN: 2110

Alfa AF: 0.680 Hom.: 1996

Bravo AF: 0.767

Asia WGS AF: 0.746 AC: 2577 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.77
DANN	Benign	0.35
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: rs1469345; hg19: chr2-231061192;