rs1405244706

Variant names:

• chr2-230207981-C-G
• rs1405244706
• NM_080424.4:c.898+10G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-230207981-C-G
• chr2-230207981-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080424.4(SP110):​c.898+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000352 in 1,420,764 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.898+10G>C		intron	N/A	NP_536349.3	Q9HB58-6
	SP110	NM_001378442.1		c.916+10G>C		intron	N/A	NP_001365371.1
	SP110	NM_001378443.1		c.898+10G>C		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.898+10G>C		intron	N/A	ENSP00000258381.6	Q9HB58-6
	SP110	ENST00000358662.9	TSL:1	c.898+10G>C		intron	N/A	ENSP00000351488.4	Q9HB58-1
	SP110	ENST00000258382.10	TSL:1	c.898+10G>C		intron	N/A	ENSP00000258382.5	Q9HB58-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000445 AC: 1 AN: 224664 AF XY: 0.00000824

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000305

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000315 AC: 4 AN: 1268534 Hom.: 0 Cov.: 18 AF XY: 0.00000469 AC XY: 3 AN XY: 639182

African (AFR) AF: 0.00 AC: 0 AN: 28990

American (AMR) AF: 0.0000232 AC: 1 AN: 43086

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24484

East Asian (EAS) AF: 0.0000518 AC: 2 AN: 38604

South Asian (SAS) AF: 0.00 AC: 0 AN: 80774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5350

European-Non Finnish (NFE) AF: 0.00000106 AC: 1 AN: 941478

Other (OTH) AF: 0.00 AC: 0 AN: 53564

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152230 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74368

African (AFR) AF: 0.0000241 AC: 1 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5208

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.12
DANN	Benign	0.68
PhyloP100		-1.8

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: rs1405244706; hg19: chr2-231072696;