rs9989746

Variant names:

• chr2-230251075-G-A
• rs9989746
• NM_007237.5:c.1057+14G>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.1057+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,608,132 control chromosomes in the GnomAD database, including 21,854 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 0.13 (1424 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20430 hom.)
• Consequence: SP140 NM_007237.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453
• Publications: 17 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP140	NM_007237.5	MANE Select	c.1057+14G>A		intron	N/A	NP_009168.4
	SP140	NM_001278451.2		c.1057+14G>A		intron	N/A	NP_001265380.1	Q13342-5
	SP140	NM_001278452.2		c.979+14G>A		intron	N/A	NP_001265381.1	Q13342-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SP140	ENST00000392045.8	TSL:2 MANE Select	c.1057+14G>A		intron	N/A	ENSP00000375899.3	Q13342-1
	SP140	ENST00000420434.7	TSL:1	c.1057+14G>A		intron	N/A	ENSP00000398210.3	Q13342-5
	SP140	ENST00000343805.10	TSL:1	c.979+14G>A		intron	N/A	ENSP00000342096.6	Q13342-6

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19228 AN: 152108 Hom.: 1423 Cov.: 32

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.132

GnomAD2 exomes AF: 0.135 AC: 33584 AN: 248388 AF XY: 0.141

Gnomad AFR exome AF: 0.0640

Gnomad AMR exome AF: 0.0995

Gnomad ASJ exome AF: 0.175

Gnomad EAS exome AF: 0.00145

Gnomad FIN exome AF: 0.104

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.162 AC: 235391 AN: 1455906 Hom.: 20430 Cov.: 29 AF XY: 0.162 AC XY: 117664 AN XY: 724470

African (AFR) AF: 0.0668 AC: 2228 AN: 33334

American (AMR) AF: 0.104 AC: 4627 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 4503 AN: 26100

East Asian (EAS) AF: 0.000807 AC: 32 AN: 39652

South Asian (SAS) AF: 0.151 AC: 13020 AN: 86076

European-Finnish (FIN) AF: 0.105 AC: 5627 AN: 53348

Middle Eastern (MID) AF: 0.199 AC: 939 AN: 4728

European-Non Finnish (NFE) AF: 0.176 AC: 195342 AN: 1107954

Other (OTH) AF: 0.151 AC: 9073 AN: 60098

GnomAD4 genome AF: 0.126 AC: 19224 AN: 152226 Hom.: 1424 Cov.: 32 AF XY: 0.122 AC XY: 9060 AN XY: 74416

African (AFR) AF: 0.0675 AC: 2805 AN: 41542

American (AMR) AF: 0.118 AC: 1808 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3472

East Asian (EAS) AF: 0.000963 AC: 5 AN: 5190

South Asian (SAS) AF: 0.139 AC: 671 AN: 4822

European-Finnish (FIN) AF: 0.101 AC: 1072 AN: 10604

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.174 AC: 11851 AN: 67986

Other (OTH) AF: 0.130 AC: 276 AN: 2116

Alfa AF: 0.155 Hom.: 425

Bravo AF: 0.122

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.61
DANN	Benign	0.52
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs9989746; hg19: chr2-231115790; COSMIC: COSV59448904;