chr2-230208022-T-C

Variant names:

• chr2-230208022-T-C
• rs200558530
• NM_080424.4:c.867A>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_080424.4(SP110):​c.867A>G​(p.Lys289Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000115 in 1,567,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: SP110 NM_080424.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0570
• 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-230208022-T-C is Benign according to our data. Variant chr2-230208022-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2770759.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.057 with no splicing effect.

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.867A>G	p.Lys289Lys	synonymous	Exon 8 of 19	NP_536349.3	Q9HB58-6
	SP110	NM_001378442.1		c.885A>G	p.Lys295Lys	synonymous	Exon 9 of 20	NP_001365371.1
	SP110	NM_001378443.1		c.867A>G	p.Lys289Lys	synonymous	Exon 8 of 19	NP_001365372.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	ENST00000258381.11	TSL:2 MANE Select	c.867A>G	p.Lys289Lys	synonymous	Exon 8 of 19	ENSP00000258381.6	Q9HB58-6
	SP110	ENST00000358662.9	TSL:1	c.867A>G	p.Lys289Lys	synonymous	Exon 8 of 18	ENSP00000351488.4	Q9HB58-1
	SP110	ENST00000258382.10	TSL:1	c.867A>G	p.Lys289Lys	synonymous	Exon 8 of 15	ENSP00000258382.5	Q9HB58-3

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.00000826 AC: 2 AN: 242124 AF XY: 0.00000764

Gnomad AFR exome AF: 0.0000647

Gnomad AMR exome AF: 0.0000294

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: 0.00000495 AC: 7 AN: 1414970 Hom.: 0 Cov.: 25 AF XY: 0.00000566 AC XY: 4 AN XY: 706372

African (AFR) AF: 0.0000619 AC: 2 AN: 32324

American (AMR) AF: 0.0000226 AC: 1 AN: 44314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25644

East Asian (EAS) AF: 0.00 AC: 0 AN: 39436

South Asian (SAS) AF: 0.00 AC: 0 AN: 84562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071504

Other (OTH) AF: 0.0000683 AC: 4 AN: 58524

GnomAD4 genome AF: 0.0000722 AC: 11 AN: 152334 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74508

African (AFR) AF: 0.000241 AC: 10 AN: 41572

American (AMR) AF: 0.0000653 AC: 1 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hepatic veno-occlusive disease-immunodeficiency syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.86
PhyloP100		-0.057
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200558530; hg19: chr2-231072737;