chr2-230202589-C-G

Variant names:

• chr2-230202589-C-G
• rs7606916
• NM_080424.4:c.1038G>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001378442.1(SP110):​c.1056G>C​(p.Ser352Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 1,614,088 control chromosomes in the GnomAD database, including 2,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S352S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.074 (1336 hom., cov: 32)
  • Exomes 𝑓: 0.0086 (1267 hom.)
• Consequence: SP110 NM_001378442.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.634
• Publications: 6 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 2-230202589-C-G is Benign according to our data. Variant chr2-230202589-C-G is described in ClinVar as Benign. ClinVar VariationId is 334907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.634 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378442.1. 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.1038G>C	p.Ser346Ser	synonymous	Exon 9 of 19	NP_536349.3
	SP110	NM_001378442.1		c.1056G>C	p.Ser352Ser	synonymous	Exon 10 of 20	NP_001365371.1
	SP110	NM_001378443.1		c.1038G>C	p.Ser346Ser	synonymous	Exon 9 of 19	NP_001365372.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	ENST00000258381.11	TSL:2 MANE Select	c.1038G>C	p.Ser346Ser	synonymous	Exon 9 of 19	ENSP00000258381.6
	SP110	ENST00000358662.9	TSL:1	c.1038G>C	p.Ser346Ser	synonymous	Exon 9 of 18	ENSP00000351488.4
	SP110	ENST00000258382.10	TSL:1	c.1038G>C	p.Ser346Ser	synonymous	Exon 9 of 15	ENSP00000258382.5

Frequencies

GnomAD3 genomes AF: 0.0741 AC: 11279 AN: 152136 Hom.: 1323 Cov.: 32

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0288

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0193

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.0544

GnomAD2 exomes AF: 0.0210 AC: 5276 AN: 251450 AF XY: 0.0157

Gnomad AFR exome AF: 0.260

Gnomad AMR exome AF: 0.0123

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.0164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000545

Gnomad OTH exome AF: 0.0101

GnomAD4 exome AF: 0.00860 AC: 12567 AN: 1461834 Hom.: 1267 Cov.: 31 AF XY: 0.00767 AC XY: 5581 AN XY: 727230

African (AFR) AF: 0.264 AC: 8827 AN: 33472

American (AMR) AF: 0.0142 AC: 635 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00168 AC: 44 AN: 26136

East Asian (EAS) AF: 0.0235 AC: 931 AN: 39698

South Asian (SAS) AF: 0.00634 AC: 547 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00850 AC: 49 AN: 5768

European-Non Finnish (NFE) AF: 0.000404 AC: 449 AN: 1111972

Other (OTH) AF: 0.0180 AC: 1085 AN: 60388

GnomAD4 genome AF: 0.0744 AC: 11335 AN: 152254 Hom.: 1336 Cov.: 32 AF XY: 0.0716 AC XY: 5330 AN XY: 74468

African (AFR) AF: 0.256 AC: 10614 AN: 41498

American (AMR) AF: 0.0287 AC: 440 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.0191 AC: 99 AN: 5182

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4826

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

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

European-Non Finnish (NFE) AF: 0.000529 AC: 36 AN: 68026

Other (OTH) AF: 0.0539 AC: 114 AN: 2116

Alfa AF: 0.00835 Hom.: 36

Bravo AF: 0.0859

Asia WGS AF: 0.0260 AC: 92 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.000771

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hepatic veno-occlusive disease-immunodeficiency syndrome (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.84
DANN	Benign	0.60
PhyloP100		-0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7606916; hg19: chr2-231067305; COSMIC: COSV51262748; COSMIC: COSV51262748;