rs41309088

Variant names:

• chr2-230212968-C-T
• rs41309088
• NM_080424.4:c.376G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-230212968-C-T
• chr2-230212968-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_080424.4(SP110):​c.376G>A​(p.Gly126Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 1,613,966 control chromosomes in the GnomAD database, including 315 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (44 hom., cov: 31)
  • Exomes 𝑓: 0.015 (271 hom.)
• Consequence: SP110 NM_080424.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.240
• Publications: 8 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=0.0027492046).
• BP6: Variant 2-230212968-C-T is Benign according to our data. Variant chr2-230212968-C-T is described in ClinVar as Benign. ClinVar VariationId is 334918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0144 (2188/152142) while in subpopulation NFE AF = 0.0171 (1165/67990). AF 95% confidence interval is 0.0163. There are 44 homozygotes in GnomAd4. There are 1172 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 44 AR gene

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.376G>A	p.Gly126Ser	missense	Exon 4 of 19	NP_536349.3	Q9HB58-6
	SP110	NM_001378442.1		c.394G>A	p.Gly132Ser	missense	Exon 5 of 20	NP_001365371.1
	SP110	NM_001378443.1		c.376G>A	p.Gly126Ser	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.376G>A	p.Gly126Ser	missense	Exon 4 of 19	ENSP00000258381.6	Q9HB58-6
	SP110	ENST00000358662.9	TSL:1	c.376G>A	p.Gly126Ser	missense	Exon 4 of 18	ENSP00000351488.4	Q9HB58-1
	SP110	ENST00000258382.10	TSL:1	c.376G>A	p.Gly126Ser	missense	Exon 4 of 15	ENSP00000258382.5	Q9HB58-3

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2188 AN: 152024 Hom.: 44 Cov.: 31

Gnomad AFR AF: 0.00191

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00643

Gnomad FIN AF: 0.0589

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0135

GnomAD2 exomes AF: 0.0163 AC: 4084 AN: 250082 AF XY: 0.0165

Gnomad AFR exome AF: 0.00215

Gnomad AMR exome AF: 0.0104

Gnomad ASJ exome AF: 0.0195

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0579

Gnomad NFE exome AF: 0.0172

Gnomad OTH exome AF: 0.0209

GnomAD4 exome AF: 0.0153 AC: 22418 AN: 1461824 Hom.: 271 Cov.: 37 AF XY: 0.0152 AC XY: 11046 AN XY: 727218

African (AFR) AF: 0.00170 AC: 57 AN: 33480

American (AMR) AF: 0.0103 AC: 460 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0210 AC: 549 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00580 AC: 500 AN: 86258

European-Finnish (FIN) AF: 0.0548 AC: 2928 AN: 53416

Middle Eastern (MID) AF: 0.00815 AC: 47 AN: 5768

European-Non Finnish (NFE) AF: 0.0153 AC: 17001 AN: 1111960

Other (OTH) AF: 0.0145 AC: 876 AN: 60392

GnomAD4 genome AF: 0.0144 AC: 2188 AN: 152142 Hom.: 44 Cov.: 31 AF XY: 0.0158 AC XY: 1172 AN XY: 74366

African (AFR) AF: 0.00190 AC: 79 AN: 41528

American (AMR) AF: 0.0114 AC: 175 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00664 AC: 32 AN: 4816

European-Finnish (FIN) AF: 0.0589 AC: 623 AN: 10582

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0171 AC: 1165 AN: 67990

Other (OTH) AF: 0.0128 AC: 27 AN: 2102

Alfa AF: 0.0150 Hom.: 67

Bravo AF: 0.00975

TwinsUK AF: 0.0200 AC: 74

ALSPAC AF: 0.0179 AC: 69

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.0170 AC: 146

ExAC AF: 0.0154 AC: 1874

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0175

EpiControl AF: 0.0210

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)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.9
DANN	Benign	0.65
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.24
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.044
Sift	Benign	0.097	T
Sift4G	Benign	0.37	T
Polyphen		0.037	B
Vest4		0.099
MPC		0.56
ClinPred		0.0071	T
GERP RS		0.90
Varity_R		0.024
gMVP		0.22
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: rs41309088; hg19: chr2-231077683; COSMIC: COSV51248582; COSMIC: COSV51248582;