2-230249416-G-A

Variant names:

• chr2-230249416-G-A
• rs9989899
• NM_007237.5:c.976+448G>A

Variant summary

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

The NM_007237.5(SP140):​c.976+448G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,110 control chromosomes in the GnomAD database, including 2,040 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 0.16 (2040 hom., cov: 32)
• Consequence: SP140 NM_007237.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.537
• Publications: 9 publications found

Genes affected

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007237.5. 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
	SP140	NM_007237.5	MANE Select	c.976+448G>A		intron	N/A	NP_009168.4
	SP140	NM_001278451.2		c.976+448G>A		intron	N/A	NP_001265380.1
	SP140	NM_001278452.2		c.898+448G>A		intron	N/A	NP_001265381.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP140	ENST00000392045.8	TSL:2 MANE Select	c.976+448G>A		intron	N/A	ENSP00000375899.3
	SP140	ENST00000420434.7	TSL:1	c.976+448G>A		intron	N/A	ENSP00000398210.3
	SP140	ENST00000343805.10	TSL:1	c.898+448G>A		intron	N/A	ENSP00000342096.6

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24157 AN: 151992 Hom.: 2037 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.163

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.159 AC: 24174 AN: 152110 Hom.: 2040 Cov.: 32 AF XY: 0.154 AC XY: 11457 AN XY: 74358

African (AFR) AF: 0.153 AC: 6352 AN: 41472

American (AMR) AF: 0.134 AC: 2041 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 616 AN: 3468

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.157 AC: 757 AN: 4826

European-Finnish (FIN) AF: 0.123 AC: 1301 AN: 10580

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12598 AN: 67984

Other (OTH) AF: 0.162 AC: 341 AN: 2108

Alfa AF: 0.175 Hom.: 1739

Bravo AF: 0.156

Asia WGS AF: 0.0660 AC: 231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.54
PhyloP100		0.54
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: rs9989899; hg19: chr2-231114131;