rs9989746

Variant names:

• chr2-230251075-G-A
• rs9989746
• NM_007237.5:c.1057+14G>A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SP140	NM_007237.5	c.1057+14G>A		intron_variant	Intron 10 of 26	ENST00000392045.8	NP_009168.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SP140	ENST00000392045.8	c.1057+14G>A		intron_variant	Intron 10 of 26	2	NM_007237.5	ENSP00000375899.3
SP140	ENST00000420434.7	c.1057+14G>A		intron_variant	Intron 10 of 25	1		ENSP00000398210.3
SP140	ENST00000343805.10	c.979+14G>A		intron_variant	Intron 9 of 24	1		ENSP00000342096.6
SP140	ENST00000417495.7	c.817+2107G>A		intron_variant	Intron 8 of 23	1		ENSP00000393618.3

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

GnomAD3 exomes AF: 0.135 AC: 33584 AN: 248388 Hom.: 2678 AF XY: 0.141 AC XY: 18965 AN XY: 134722

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 SAS exome AF: 0.151

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

Gnomad4 AFR exome AF: 0.0668

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.000807

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.176

Gnomad4 OTH exome AF: 0.151

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

Gnomad4 AFR AF: 0.0675

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.130

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.61
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs9989746; hg19: chr2-231115790; COSMIC: COSV59448904;