2-230225228-T-C

Position:

• chr2-230225228-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378442.1(SP110):​c.-64+307A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,238 control chromosomes in the GnomAD database, including 1,529 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 0.13 (1529 hom., cov: 32)
• Consequence: SP110 NM_001378442.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP110	NM_001185015.2	c.-64+307A>G		intron_variant			NP_001171944.1
SP110	NM_001378442.1	c.-64+307A>G		intron_variant			NP_001365371.1
SP110	NM_001378444.1	c.-64+307A>G		intron_variant			NP_001365373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP140	ENST00000456542.5	c.-90-527T>C		intron_variant		4		ENSP00000475284
SP110	ENST00000540870.5	c.-64+307A>G		intron_variant		2		ENSP00000439558

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20413 AN: 152120 Hom.: 1528 Cov.: 32

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.134 AC: 20410 AN: 152238 Hom.: 1529 Cov.: 32 AF XY: 0.130 AC XY: 9642 AN XY: 74450

Gnomad4 AFR AF: 0.0897

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.135

Alfa AF: 0.170 Hom.: 3791

Bravo AF: 0.131

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.5
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10209615; hg19: chr2-231089943;