rs1427294

Variant names:

• chr2-230213733-G-A
• rs1427294
• NM_080424.4:c.317-706C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-230213733-G-A
• chr2-230213733-G-C

Variant summary

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

The NM_080424.4(SP110):​c.317-706C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.915 in 152,632 control chromosomes in the GnomAD database, including 63,984 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 0.91 (63864 hom., cov: 33)
  • Exomes 𝑓: 0.81 (120 hom.)
• Consequence: SP110 NM_080424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	NM_080424.4	MANE Select	c.317-706C>T		intron	N/A	NP_536349.3
	SP110	NM_001378442.1		c.335-706C>T		intron	N/A	NP_001365371.1
	SP110	NM_001378443.1		c.317-706C>T		intron	N/A	NP_001365372.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	ENST00000258381.11	TSL:2 MANE Select	c.317-706C>T		intron	N/A	ENSP00000258381.6
	SP110	ENST00000358662.9	TSL:1	c.317-706C>T		intron	N/A	ENSP00000351488.4
	SP110	ENST00000258382.10	TSL:1	c.317-706C>T		intron	N/A	ENSP00000258382.5

Frequencies

GnomAD3 genomes AF: 0.915 AC: 139202 AN: 152160 Hom.: 63811 Cov.: 33

Gnomad AFR AF: 0.972

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.879

Gnomad OTH AF: 0.911

GnomAD4 exome AF: 0.814 AC: 288 AN: 354 Hom.: 120 Cov.: 0 AF XY: 0.804 AC XY: 156 AN XY: 194

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AF: 0.875 AC: 28 AN: 32

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.900 AC: 9 AN: 10

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.796 AC: 234 AN: 294

Other (OTH) AF: 0.929 AC: 13 AN: 14

GnomAD4 genome AF: 0.915 AC: 139313 AN: 152278 Hom.: 63864 Cov.: 33 AF XY: 0.916 AC XY: 68171 AN XY: 74462

African (AFR) AF: 0.972 AC: 40410 AN: 41570

American (AMR) AF: 0.918 AC: 14046 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 3211 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5155 AN: 5168

South Asian (SAS) AF: 0.942 AC: 4544 AN: 4822

European-Finnish (FIN) AF: 0.867 AC: 9196 AN: 10604

Middle Eastern (MID) AF: 0.921 AC: 269 AN: 292

European-Non Finnish (NFE) AF: 0.879 AC: 59759 AN: 68022

Other (OTH) AF: 0.910 AC: 1921 AN: 2112

Alfa AF: 0.900 Hom.: 16427

Bravo AF: 0.921

Asia WGS AF: 0.961 AC: 3342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.40
PhyloP100		0.025
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: rs1427294; hg19: chr2-231078448;