rs11556887

Variant names:

• chr2-230212961-G-A
• rs11556887
• NM_080424.4:c.383C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_080424.4(SP110):​c.383C>T​(p.Ala128Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0965 in 1,613,944 control chromosomes in the GnomAD database, including 9,150 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.077 (584 hom., cov: 31)
  • Exomes 𝑓: 0.099 (8566 hom.)
• Consequence: SP110 NM_080424.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.128
• Publications: 32 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004897028).
• BP6: Variant 2-230212961-G-A is Benign according to our data. Variant chr2-230212961-G-A is described in ClinVar as Benign. ClinVar VariationId is 334917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.222 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP110	NM_080424.4	MANE Select	c.383C>T	p.Ala128Val	missense	Exon 4 of 19	NP_536349.3	Q9HB58-6
	SP110	NM_001378442.1		c.401C>T	p.Ala134Val	missense	Exon 5 of 20	NP_001365371.1
	SP110	NM_001378443.1		c.383C>T	p.Ala128Val	missense	Exon 4 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.383C>T	p.Ala128Val	missense	Exon 4 of 19	ENSP00000258381.6	Q9HB58-6
	SP110	ENST00000358662.9	TSL:1	c.383C>T	p.Ala128Val	missense	Exon 4 of 18	ENSP00000351488.4	Q9HB58-1
	SP110	ENST00000258382.10	TSL:1	c.383C>T	p.Ala128Val	missense	Exon 4 of 15	ENSP00000258382.5	Q9HB58-3

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11680 AN: 152052 Hom.: 585 Cov.: 31

Gnomad AFR AF: 0.0253

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0588

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0831

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.0611

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0981

Gnomad OTH AF: 0.0810

GnomAD2 exomes AF: 0.102 AC: 25538 AN: 250300 AF XY: 0.111

Gnomad AFR exome AF: 0.0275

Gnomad AMR exome AF: 0.0411

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.0992

Gnomad FIN exome AF: 0.0613

Gnomad NFE exome AF: 0.0983

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.0986 AC: 144096 AN: 1461774 Hom.: 8566 Cov.: 37 AF XY: 0.104 AC XY: 75459 AN XY: 727192

African (AFR) AF: 0.0259 AC: 867 AN: 33480

American (AMR) AF: 0.0451 AC: 2019 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4233 AN: 26136

East Asian (EAS) AF: 0.0861 AC: 3418 AN: 39688

South Asian (SAS) AF: 0.229 AC: 19709 AN: 86254

European-Finnish (FIN) AF: 0.0626 AC: 3344 AN: 53416

Middle Eastern (MID) AF: 0.160 AC: 920 AN: 5764

European-Non Finnish (NFE) AF: 0.0929 AC: 103314 AN: 1111920

Other (OTH) AF: 0.104 AC: 6272 AN: 60392

GnomAD4 genome AF: 0.0767 AC: 11668 AN: 152170 Hom.: 584 Cov.: 31 AF XY: 0.0780 AC XY: 5805 AN XY: 74414

African (AFR) AF: 0.0252 AC: 1048 AN: 41524

American (AMR) AF: 0.0587 AC: 898 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 555 AN: 3466

East Asian (EAS) AF: 0.0831 AC: 429 AN: 5164

South Asian (SAS) AF: 0.234 AC: 1126 AN: 4820

European-Finnish (FIN) AF: 0.0611 AC: 648 AN: 10608

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0981 AC: 6672 AN: 67984

Other (OTH) AF: 0.0806 AC: 170 AN: 2108

Alfa AF: 0.0960 Hom.: 2230

Bravo AF: 0.0706

TwinsUK AF: 0.0944 AC: 350

ALSPAC AF: 0.0877 AC: 338

ESP6500AA AF: 0.0279 AC: 123

ESP6500EA AF: 0.0936 AC: 805

ExAC AF: 0.104 AC: 12624

Asia WGS AF: 0.135 AC: 468 AN: 3478

EpiCase AF: 0.0985

EpiControl AF: 0.0985

ClinVar

ClinVar submissions

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)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.13
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.062
Sift	Benign	0.060	T
Sift4G	Benign	0.42	T
Polyphen		1.0	D
Vest4		0.11
MPC		0.41
ClinPred		0.011	T
GERP RS		-1.1
Varity_R		0.026
gMVP		0.44
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: rs11556887; hg19: chr2-231077676; COSMIC: COSV51247734; COSMIC: COSV51247734;