rs28445040

Positions:

• chr2-230245867-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007237.5(SP140):​c.669C>T​(p.Ser223=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,594,098 control chromosomes in the GnomAD database, including 24,594 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 0.15 (1844 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22750 hom.)
• Consequence: SP140 NM_007237.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-0.109 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP140	NM_007237.5	c.669C>T	p.Ser223=	synonymous_variant	7/27	ENST00000392045.8	NP_009168.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SP140	ENST00000392045.8	c.669C>T	p.Ser223=	synonymous_variant	7/27	2	NM_007237.5	ENSP00000375899	A2
SP140	ENST00000420434.7	c.669C>T	p.Ser223=	synonymous_variant	7/26	1		ENSP00000398210	A2
SP140	ENST00000417495.7	c.660C>T	p.Ser220=	synonymous_variant	7/24	1		ENSP00000393618	P2
SP140	ENST00000343805.10	c.664+787C>T		intron_variant		1		ENSP00000342096	A2

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22740 AN: 152100 Hom.: 1842 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.151

GnomAD3 exomes AF: 0.149 AC: 37104 AN: 248796 Hom.: 3167 AF XY: 0.155 AC XY: 20942 AN XY: 134978

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.105

Gnomad ASJ exome AF: 0.187

Gnomad EAS exome AF: 0.00251

Gnomad SAS exome AF: 0.171

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.172 AC: 247608 AN: 1441880 Hom.: 22750 Cov.: 28 AF XY: 0.173 AC XY: 124182 AN XY: 718368

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.183

Gnomad4 EAS exome AF: 0.00129

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.149 AC: 22745 AN: 152218 Hom.: 1844 Cov.: 32 AF XY: 0.145 AC XY: 10781 AN XY: 74432

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.150

Alfa AF: 0.181 Hom.: 3291

Bravo AF: 0.145

Asia WGS AF: 0.0640 AC: 225 AN: 3478

EpiCase AF: 0.188

EpiControl AF: 0.185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs28445040; hg19: chr2-231110582;