2-230217219-C-T

Variant names:

• chr2-230217219-C-T
• rs1966555
• NM_080424.4:c.-1-291G>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.-1-291G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.50 (18198 hom., cov: 20)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.745
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP110	NM_080424.4	c.-1-291G>A		intron_variant	Intron 1 of 18	ENST00000258381.11	NP_536349.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP110	ENST00000258381.11	c.-1-291G>A		intron_variant	Intron 1 of 18	2	NM_080424.4	ENSP00000258381.6

Frequencies

GnomAD3 genomes AF: 0.500 AC: 71737 AN: 143558 Hom.: 18193 Cov.: 20

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.422

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.500 AC: 71764 AN: 143636 Hom.: 18198 Cov.: 20 AF XY: 0.501 AC XY: 34793 AN XY: 69408

African (AFR) AF: 0.605 AC: 22959 AN: 37946

American (AMR) AF: 0.419 AC: 5955 AN: 14226

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1631 AN: 3436

East Asian (EAS) AF: 0.404 AC: 1958 AN: 4852

South Asian (SAS) AF: 0.478 AC: 2164 AN: 4526

European-Finnish (FIN) AF: 0.573 AC: 5076 AN: 8864

Middle Eastern (MID) AF: 0.426 AC: 116 AN: 272

European-Non Finnish (NFE) AF: 0.458 AC: 30513 AN: 66664

Other (OTH) AF: 0.474 AC: 930 AN: 1960

Alfa AF: 0.494 Hom.: 2326

Bravo AF: 0.494

Asia WGS AF: 0.445 AC: 1550 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.74
PhyloP100		-0.74
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: rs1966555; hg19: chr2-231081934;